Cheryl H. Arrowsmith

Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.

Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D, Li Y, Kwon D, Tan R, Wilson RP, Leopold K, Subramaniam S, Halabelian L, Arrowsmith CH, Bénard F
Nat Chem Biol. 2022 . doi: 10.1038/s41589-022-01059-7
PMID: 35676539

PRMT inhibition induces a viral mimicry response in triple-negative breast cancer.

Wu Q, Nie DY, Ba-Alawi W, Ji Y, Zhang Z, Cruickshank J, Haight J, Ciamponi FE, Chen J, Duan S, Shen Y, Liu J, Marhon SA, Mehdipour P, Szewczyk MM, Dogan-Artun N, Chen W, Zhang LX, Deblois G, Prinos P, Massirer KB, Barsyte-Lovejoy D, Jin J, De Carvalho DD, Haibe-Kains B, Wang X, Cescon DW, Lupien M, Arrowsmith CH
Nat Chem Biol. 2022 . doi: 10.1038/s41589-022-01024-4
PMID: 35578032

A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization.

Dilworth D, Hanley RP, Ferreira de Freitas R, Allali-Hassani A, Zhou M, Mehta N, Marunde MR, Ackloo S, Carvalho Machado RA, Khalili Yazdi A, Owens DDG, Vu V, Nie DY, Alqazzaz M, Marcon E, Li F, Chau I, Bolotokova A, Qin S, Lei M, Liu Y, Szewczyk MM, Dong A, Kazemzadeh S, Abramyan T, Popova IK, Hall NW, Meiners MJ, Cheek MA, Gibson E, Kireev D, Greenblatt JF, Keogh MC, Min J, Brown PJ, Vedadi M, Arrowsmith CH, Barsyte-Lovejoy D, James LI, Schapira M
Nat Chem Biol. 2021 . doi: 10.1038/s41589-021-00898-0
PMID: 34782742

PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Sachamitr P, Ho JC, Ciamponi FE, Ba-Alawi W, Coutinho FJ, Guilhamon P, Kushida MM, Cavalli FMG, Lee L, Rastegar N, Vu V, Sánchez-Osuna M, Coulombe-Huntington J, Kanshin E, Whetstone H, Durand M, Thibault P, Hart K, Mangos M, Veyhl J, Chen W, Tran N, Duong BC, Aman AM, Che X, Lan X, Whitley O, Zaslaver O, Barsyte-Lovejoy D, Richards LM, Restall I, Caudy A, Röst HL, Bonday ZQ, Bernstein M, Das S, Cusimano MD, Spears J, Bader GD, Pugh TJ, Tyers M, Lupien M, Haibe-Kains B, Artee Luchman H, Weiss S, Massirer KB, Prinos P, Arrowsmith CH, Dirks PB
Nat Commun. 2021 12(1):979. doi: 10.1038/s41467-021-21204-5
PMID: 33579912

GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer.

Wu Q, Ba-Alawi W, Deblois G, Cruickshank J, Duan S, Lima-Fernandes E, Haight J, Tonekaboni SAM, Fortier AM, Kuasne H, McKee TD, Mahmoud H, Kushida M, Cameron S, Dogan-Artun N, Chen W, Nie Y, Zhang LX, Vellanki RN, Zhou S, Prinos P, Wouters BG, Dirks PB, Done SJ, Park M, Cescon DW, Haibe-Kains B, Lupien M, Arrowsmith CH
Nat Commun. 2020 11(1):4205. doi: 10.1038/s41467-020-18020-8
PMID: 32826891

Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3.

Böttcher J, Dilworth D, Reiser U, Neumüller RA, Schleicher M, Petronczki M, Zeeb M, Mischerikow N, Allali-Hassani A, Szewczyk MM, Li F, Kennedy S, Vedadi M, Barsyte-Lovejoy D, Brown PJ, Huber KVM, Rogers CM, Wells CI, Fedorov O, Rumpel K, Zoephel A, Mayer M, Wunberg T, Böse D, Zahn S, Arnhof H, Berger H, Reiser C, Hörmann A, Krammer T, Corcokovic M, Sharps B, Winkler S, Häring D, Cockcroft XL, Fuchs JE, Müllauer B, Weiss-Puxbaum A, Gerstberger T, Boehmelt G, Vakoc CR, Arrowsmith CH, Pearson M, McConnell DB
Nat. Chem. Biol.. 2019 . doi: 10.1038/s41589-019-0310-x
PMID: 31285596

Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition.

Halabelian L, Ravichandran M, Li Y, Zeng H, Rao A, Aravind L, Arrowsmith CH
Nat. Struct. Mol. Biol.. 2019 . doi: 10.1038/s41594-019-0246-6
PMID: 31235913

Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells.

Lima-Fernandes E, Murison A, da Silva Medina T, Wang Y, Ma A, Leung C, Luciani GM, Haynes J, Pollett A, Zeller C, Duan S, Kreso A, Barsyte-Lovejoy D, Wouters BG, Jin J, Carvalho DD, Lupien M, Arrowsmith CH, O'Brien CA
Nat Commun. 2019 10(1):1436. doi: 10.1038/s41467-019-09309-4
PMID: 30926792

Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy.

Lan X, Jörg DJ, Cavalli FMG, Richards LM, Nguyen LV, Vanner RJ, Guilhamon P, Lee L, Kushida MM, Pellacani D, Park NI, Coutinho FJ, Whetstone H, Selvadurai HJ, Che C, Luu B, Carles A, Moksa M, Rastegar N, Head R, Dolma S, Prinos P, Cusimano MD, Das S, Bernstein M, Arrowsmith CH, Mungall AJ, Moore RA, Ma Y, Gallo M, Lupien M, Pugh TJ, Taylor MD, Hirst M, Eaves CJ, Simons BD, Dirks PB
Nature. 2017 . doi: 10.1038/nature23666
PMID: 28854171

Global analysis of protein folding using massively parallel design, synthesis, and testing.

Rocklin GJ, Chidyausiku TM, Goreshnik I, Ford A, Houliston S, Lemak A, Carter L, Ravichandran R, Mulligan VK, Chevalier A, Arrowsmith CH, Baker D
Science. 2017 357(6347):168-175. doi: 10.1126/science.aan0693
PMID: 28706065

The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex.

He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J, Lima-Fernandes E, Szewczyk MM, Cheng D, Klinge KL, Li HQ, Pliushchev M, Algire MA, Maag D, Guo J, Dietrich J, Panchal SC, Petros AM, Sweis RF, Torrent M, Bigelow LJ, Senisterra G, Li F, Kennedy S, Wu Q, Osterling DJ, Lindley DJ, Gao W, Galasinski S, Barsyte-Lovejoy D, Vedadi M, Buchanan FG, Arrowsmith CH, Chiang GG, Sun C, Pappano WN
Nat. Chem. Biol.. 2017 . doi: 10.1038/nchembio.2306
PMID: 28135237

Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma.

Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, Lam N, Souza BK, Giannini G, Hager GL, Arrowsmith CH, Khan J, Appella E, Thiele CJ
Cancer Cell. 2017 31(1):50-63. doi: 10.1016/j.ccell.2016.12.002
PMID: 28073004

Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth.

Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, Barsyte-Lovejoy D, Al-awar R, Katona BW, Shilatifard A, Huang J, Hua X, Arrowsmith CH, Berger SL
Nature. 2015 525(7568):206-11. doi: 10.1038/nature15251
PMID: 26331536

The promise and peril of chemical probes.

Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ
Nat. Chem. Biol.. 2015 11(8):536-41. doi: 10.1038/nchembio.1867
PMID: 26196764

Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.

Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KV, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G
Nat. Chem. Biol.. 2015 . doi: 10.1038/nchembio.1859
PMID: 26167872

RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.

Ni Z, Xu C, Guo X, Hunter GO, Kuznetsova OV, Tempel W, Marcon E, Zhong G, Guo H, Kuo WH, Li J, Young P, Olsen JB, Wan C, Loppnau P, El Bakkouri M, Senisterra GA, He H, Huang H, Sidhu SS, Emili A, Murphy S, Mosley AL, Arrowsmith CH, Min J, Greenblatt JF
Nat. Struct. Mol. Biol.. 2014 . doi: 10.1038/nsmb.2853
PMID: 24997600

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain.

James LI, Barsyte-Lovejoy D, Zhong N, Krichevsky L, Korboukh VK, Herold JM, Macnevin CJ, Norris JL, Sagum CA, Tempel W, Marcon E, Guo H, Gao C, Huang XP, Duan S, Emili A, Greenblatt JF, Kireev DB, Jin J, Janzen WP, Brown PJ, Bedford MT, Arrowsmith CH, Frye SV
Nat. Chem. Biol.. 2013 . doi: 10.1038/nchembio.1157
PMID: 23292653

Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.

Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M
Nat Commun. 2012 3:1288. doi: 10.1038/ncomms2304
PMID: 23250418

Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation.

Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S, Badeaux AI, Barsyte-Lovejoy D, Martinez JY, Bedford MT, Fuchs SM, Arrowsmith CH, Strahl BD
Nat. Struct. Mol. Biol.. 2012 19(11):1155-60. doi: 10.1038/nsmb.2391
PMID: 23022729

Histone recognition and large-scale structural analysis of the human bromodomain family.

Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Müller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S
Cell. 2012 149(1):214-31. doi: 10.1016/j.cell.2012.02.013
PMID: 22464331

A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells.

Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J
Nat. Chem. Biol.. 2011 7(8):566-74. doi: 10.1038/nchembio.599
PMID: 21743462

Molecular basis of Pirh2-mediated p53 ubiquitylation

Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH
Nat Struct Mol Biol.. 2008 15(12):1334-42. doi: 10.1038/nsmb.1521
PMID: 19043414

L3MBTL1 recognition of mono- and dimethylated histones.

Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M, Arrowsmith CH
Nat. Struct. Mol. Biol.. 2007 14(12):1229-30. doi: 10.1038/nsmb1340
PMID: 18026117

2023

RAS and PP2A activities converge on epigenetic gene regulation.

Aakula A, Sharma M, Tabaro F, Nätkin R, Kamila J, Honkanen H, Schapira M, Arrowsmith C, Nykter M, Westermarck J
Life Sci Alliance. 02.03.2023 6(5):. doi: 10.26508/lsa.202301928
PMID: 36858798

Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21.

Göricke F, Vu V, Smith L, Scheib U, Böhm R, Akkilic N, Wohlfahrt G, Weiske J, Bömer U, Brzezinka K, Lindner N, Lienau P, Gradl S, Beck H, Brown PJ, Santhakumar V, Vedadi M, Barsyte-Lovejoy D, Arrowsmith CH, Schmees N, Petersen K
J Med Chem. 20.02.2023 . doi: 10.1021/acs.jmedchem.2c01933
PMID: 36802665

Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei.

MacDonald KM, Nicholson-Puthenveedu S, Tageldein MM, Khasnis S, Arrowsmith CH, Harding SM
Nat Commun. 02.02.2023 14(1):556. doi: 10.1038/s41467-023-36195-8
PMID: 36732527

2022

Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease.

Payliss BJ, Tse YWE, Reichheld SE, Lemak A, Yun HY, Houliston S, Patel A, Arrowsmith CH, Sharpe S, Wyatt HDM
Cell Rep. 25.10.2022 41(4):111537. doi: 10.1016/j.celrep.2022.111537
PMID: 36288699

PBRM1, SETD2 and BAP1 - the trinity of 3p in clear cell renal cell carcinoma.

Walton J, Lawson K, Prinos P, Finelli A, Arrowsmith C, Ailles L
Nat Rev Urol. 17.10.2022 . doi: 10.1038/s41585-022-00659-1
PMID: 36253570

Dissecting the stability determinants of a challenging de novo protein fold using massively parallel design and experimentation.

Kim TE, Tsuboyama K, Houliston S, Martell CM, Phoumyvong CM, Lemak A, Haddox HK, Arrowsmith CH, Rocklin GJ
Proc Natl Acad Sci U S A. 11.10.2022 119(41):e2122676119. doi: 10.1073/pnas.2122676119
PMID: 36191185

De novo design of immunoglobulin-like domains.

Chidyausiku TM, Mendes SR, Klima JC, Nadal M, Eckhard U, Roel-Touris J, Houliston S, Guevara T, Haddox HK, Moyer A, Arrowsmith CH, Gomis-Rüth FX, Baker D, Marcos E
Nat Commun. 03.10.2022 13(1):5661. doi: 10.1038/s41467-022-33004-6
PMID: 36192397

Combinatorial Anticancer Drug Screen Identifies Off-Target Effects of Epigenetic Chemical Probes.

Barghout SH, Mann MK, Aman A, Yu Y, Alteen MG, Schimmer AD, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D
ACS Chem Biol. 09.09.2022 . doi: 10.1021/acschembio.2c00451
PMID: 36084291

Enzymatic nucleosome acetylation selectively affects activity of histone methyltransferases in vitro.

Trush VV, Feller C, Li ASM, Allali-Hassani A, Szewczyk MM, Chau I, Eram MS, Jiang B, Luu R, Zhang F, Barsyte-Lovejoy D, Aebersold R, Arrowsmith CH, Vedadi M
Biochim Biophys Acta Gene Regul Mech. 27.07.2022 194845. doi: 10.1016/j.bbagrm.2022.194845
PMID: 35907431

CACHE (Critical Assessment of Computational Hit-finding Experiments): A public-private partnership benchmarking initiative to enable the development of computational methods for hit-finding.

Ackloo S, Al-Awar R, Amaro RE, Arrowsmith CH, Azevedo H, Batey RA, Bengio Y, Betz UAK, Bologa CG, Chodera JD, Cornell WD, Dunham I, Ecker GF, Edfeldt K, Edwards AM, Gilson MK, Gordijo CR, Hessler G, Hillisch A, Hogner A, Irwin JJ, Jansen JM, Kuhn D, Leach AR, Lee AA, Lessel U, Morgan MR, Moult J, Muegge I, Oprea TI, Perry BG, Riley P, Rousseaux SAL, Saikatendu KS, Santhakumar V, Schapira M, Scholten C, Todd MH, Vedadi M, Volkamer A, Willson TM
Nat Rev Chem. 06.07.2022 6(4):287-295. doi: 10.1038/s41570-022-00363-z
PMID: 35783295

Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.

Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D, Li Y, Kwon D, Tan R, Wilson RP, Leopold K, Subramaniam S, Halabelian L, Arrowsmith CH, Bénard F
Nat Chem Biol. 08.06.2022 . doi: 10.1038/s41589-022-01059-7
PMID: 35676539

PRMT inhibition induces a viral mimicry response in triple-negative breast cancer.

Wu Q, Nie DY, Ba-Alawi W, Ji Y, Zhang Z, Cruickshank J, Haight J, Ciamponi FE, Chen J, Duan S, Shen Y, Liu J, Marhon SA, Mehdipour P, Szewczyk MM, Dogan-Artun N, Chen W, Zhang LX, Deblois G, Prinos P, Massirer KB, Barsyte-Lovejoy D, Jin J, De Carvalho DD, Haibe-Kains B, Wang X, Cescon DW, Lupien M, Arrowsmith CH
Nat Chem Biol. 16.05.2022 . doi: 10.1038/s41589-022-01024-4
PMID: 35578032

Validating Small Molecule Chemical Probes for Biological Discovery.

Vu V, Szewczyk MM, Nie DY, Arrowsmith CH, Barsyte-Lovejoy D
Annu Rev Biochem. 01.04.2022 . doi: 10.1146/annurev-biochem-032620-105344
PMID: 35363509

PRMT5 regulates ATF4 transcript splicing and oxidative stress response.

Szewczyk MM, Luciani GM, Vu V, Murison A, Dilworth D, Barghout SH, Lupien M, Arrowsmith CH, Minden MD, Barsyte-Lovejoy D
Redox Biol. 11.03.2022 51:102282. doi: 10.1016/j.redox.2022.102282
PMID: 35305370

The MYC oncoprotein directly interacts with its chromatin cofactor PNUTS to recruit PP1 phosphatase.

Wei Y, Redel C, Ahlner A, Lemak A, Johansson-Åkhe I, Houliston S, Kenney TMG, Tamachi A, Morad V, Duan S, Andrews DW, Wallner B, Sunnerhagen M, Arrowsmith CH, Penn LZ
Nucleic Acids Res. 04.03.2022 . doi: 10.1093/nar/gkac138
PMID: 35244724

Target 2035 - update on the quest for a probe for every protein.

Müller S, Ackloo S, Al Chawaf A, Al-Lazikani B, Antolin A, Baell JB, Beck H, Beedie S, Betz UAK, Bezerra GA, Brennan PE, Brown D, Brown PJ, Bullock AN, Carter AJ, Chaikuad A, Chaineau M, Ciulli A, Collins I, Dreher J, Drewry D, Edfeldt K, Edwards AM, Egner U, Frye SV, Fuchs SM, Hall MD, Hartung IV, Hillisch A, Hitchcock SH, Homan E, Kannan N, Kiefer JR, Knapp S, Kostic M, Kubicek S, Leach AR, Lindemann S, Marsden BD, Matsui H, Meier JL, Merk D, Michel M, Morgan MR, Mueller-Fahrnow A, Owen DR, Perry BG, Rosenberg SH, Saikatendu KS, Schapira M, Scholten C, Sharma S, Simeonov A, Sundström M, Superti-Furga G, Todd MH, Tredup C, Vedadi M, von Delft F, Willson TM, Winter GE, Workman P, Arrowsmith CH
RSC Med Chem. 27.01.2022 13(1):13-21. doi: 10.1039/d1md00228g
PMID: 35211674

2021

Prediction and Validation of a Protein's Free Energy Surface Using Hydrogen Exchange and (Importantly) Its Denaturant Dependence.

Peng X, Baxa M, Faruk N, Sachleben JR, Pintscher S, Gagnon IA, Houliston S, Arrowsmith CH, Freed KF, Rocklin GJ, Sosnick TR
J Chem Theory Comput. 22.12.2021 . doi: 10.1021/acs.jctc.1c00960
PMID: 34936354

Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.

Harding RJ, Deme JC, Hevler JF, Tamara S, Lemak A, Cantle JP, Szewczyk MM, Begeja N, Goss S, Zuo X, Loppnau P, Seitova A, Hutchinson A, Fan L, Truant R, Schapira M, Carroll JB, Heck AJR, Lea SM, Arrowsmith CH
Commun Biol. 08.12.2021 4(1):1374. doi: 10.1038/s42003-021-02895-4
PMID: 34880419

A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization.

Dilworth D, Hanley RP, Ferreira de Freitas R, Allali-Hassani A, Zhou M, Mehta N, Marunde MR, Ackloo S, Carvalho Machado RA, Khalili Yazdi A, Owens DDG, Vu V, Nie DY, Alqazzaz M, Marcon E, Li F, Chau I, Bolotokova A, Qin S, Lei M, Liu Y, Szewczyk MM, Dong A, Kazemzadeh S, Abramyan T, Popova IK, Hall NW, Meiners MJ, Cheek MA, Gibson E, Kireev D, Greenblatt JF, Keogh MC, Min J, Brown PJ, Vedadi M, Arrowsmith CH, Barsyte-Lovejoy D, James LI, Schapira M
Nat Chem Biol. 15.11.2021 . doi: 10.1038/s41589-021-00898-0
PMID: 34782742

The human pseudouridine synthase PUS7 recognizes RNA with an extended multi-domain binding surface.

Guegueniat J, Halabelian L, Zeng H, Dong A, Li Y, Wu H, Arrowsmith CH, Kothe U
Nucleic Acids Res. 28.10.2021 . doi: 10.1093/nar/gkab934
PMID: 34718722

Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells.

Saraon P, Snider J, Schormann W, Rai A, Radulovich N, Sánchez-Osuna M, Coulombe-Huntington J, Huard C, Mohammed M, Lima-Fernandes E, Thériault B, Halabelian L, Chan M, Joshi D, Drecun L, Yao Z, Pathmanathan S, Wong V, Lyakisheva A, Aboualizadeh F, Niu L, Li F, Kiyota T, Subramanian R, Joseph B, Aman A, Prakesch M, Isaac M, Mamai A, Poda G, Vedadi M, Marcellus R, Uehling D, Leighl N, Sacher A, Samaržija M, Jakopović M, Arrowsmith C, Tyers M, Tsao MS, Andrews D, Al-Awar R, Stagljar I
J Mol Biol. 16.10.2021 433(23):167294. doi: 10.1016/j.jmb.2021.167294
PMID: 34662547

Structure-Activity Relationship of USP5 Inhibitors.

Mann MK, Zepeda-Velázquez CA, González-Álvarez H, Dong A, Kiyota T, Aman AM, Loppnau P, Li Y, Wilson B, Arrowsmith CH, Al-Awar R, Harding RJ, Schapira M
J Med Chem. 14.10.2021 . doi: 10.1021/acs.jmedchem.1c00889
PMID: 34648286

MYC protein interactors in gene transcription and cancer.

Lourenco C, Resetca D, Redel C, Lin P, MacDonald AS, Ciaccio R, Kenney TMG, Wei Y, Andrews DW, Sunnerhagen M, Arrowsmith CH, Raught B, Penn LZ
Nat Rev Cancer. 29.06.2021 . doi: 10.1038/s41568-021-00367-9
PMID: 34188192

Discovery of the SMYD3 Inhibitor BAY-6035 Using Thermal Shift Assay (TSA)-Based High-Throughput Screening.

Gradl S, Steuber H, Weiske J, Szewczyk MM, Schmees N, Siegel S, Stoeckigt D, Christ CD, Li F, Organ S, Abbey M, Kennedy S, Chau I, Trush V, Barsyte-Lovejoy D, Brown PJ, Vedadi M, Arrowsmith C, Husemann M, Badock V, Bauser M, Haegebarth A, Hartung IV, Stresemann C
SLAS Discov. 21.06.2021 24725552211019409. doi: 10.1177/24725552211019409
PMID: 34154424

Identifying and Validating MYC:Protein Interactors in Pursuit of Novel Anti-MYC Therapies.

Resetca D, MacDonald AS, Kenney TMG, Wei Y, Arrowsmith CH, Raught B, Penn LZ
Methods Mol Biol. 22.05.2021 2318:45-67. doi: 10.1007/978-1-0716-1476-1_4
PMID: 34019286

Design, Synthesis, and Evaluation of WD-Repeat-Containing Protein 5 (WDR5) Degraders.

Dölle A, Adhikari B, Krämer A, Weckesser J, Berner N, Berger LM, Diebold M, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Gebel J, Löhr F, Dötsch V, Eilers M, Heinzlmeir S, Kuster B, Sotriffer C, Wolf E, Knapp S
J Med Chem. 13.05.2021 . doi: 10.1021/acs.jmedchem.1c00146
PMID: 33980013

Protein arginine methylation: from enigmatic functions to therapeutic targeting.

Wu Q, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D
Nat Rev Drug Discov. 19.03.2021 . doi: 10.1038/s41573-021-00159-8
PMID: 33742187

A First-in-Class, Highly Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 6.

Shen Y, Li F, Szewczyk MM, Halabelian L, Chau I, Eram MS, Dela Seña C, Park KS, Meng F, Chen H, Zeng H, McLeod D, Zepeda-Velázquez CA, Campbell RM, Mader MM, Watson BM, Schapira M, Arrowsmith CH, Al-Awar R, Barsyte-Lovejoy D, Kaniskan HÜ, Brown PJ, Vedadi M, Jin J
J Med Chem. 16.02.2021 . doi: 10.1021/acs.jmedchem.0c02160
PMID: 33591753

A Semi-automated Organoid Screening Method Demonstrates Epigenetic Control of Intestinal Epithelial Differentiation.

Ostrop J, Zwiggelaar RT, Terndrup Pedersen M, Gerbe F, Bösl K, Lindholm HT, Díez-Sánchez A, Parmar N, Radetzki S, von Kries JP, Jay P, Jensen KB, Arrowsmith C, Oudhoff MJ
Front Cell Dev Biol. 13.02.2021 8:618552. doi: 10.3389/fcell.2020.618552
PMID: 33575256

PRMT5 inhibition disrupts splicing and stemness in glioblastoma.

Sachamitr P, Ho JC, Ciamponi FE, Ba-Alawi W, Coutinho FJ, Guilhamon P, Kushida MM, Cavalli FMG, Lee L, Rastegar N, Vu V, Sánchez-Osuna M, Coulombe-Huntington J, Kanshin E, Whetstone H, Durand M, Thibault P, Hart K, Mangos M, Veyhl J, Chen W, Tran N, Duong BC, Aman AM, Che X, Lan X, Whitley O, Zaslaver O, Barsyte-Lovejoy D, Richards LM, Restall I, Caudy A, Röst HL, Bonday ZQ, Bernstein M, Das S, Cusimano MD, Spears J, Bader GD, Pugh TJ, Tyers M, Lupien M, Haibe-Kains B, Artee Luchman H, Weiss S, Massirer KB, Prinos P, Arrowsmith CH, Dirks PB
Nat Commun. 12.02.2021 12(1):979. doi: 10.1038/s41467-021-21204-5
PMID: 33579912

Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2.

Ferreira de Freitas R, Liu Y, Szewczyk MM, Mehta N, Li F, McLeod D, Zepeda-Velázquez C, Dilworth D, Hanley RP, Gibson E, Brown PJ, Al-Awar R, James LI, Arrowsmith CH, Barsyte-Lovejoy D, Min J, Vedadi M, Schapira M, Allali-Hassani A
J Med Chem. 01.02.2021 . doi: 10.1021/acs.jmedchem.0c01768
PMID: 33522809

Rational Design and Synthesis of Selective PRMT4 Inhibitors: a New Chemotype for Development of Cancer Therapeutics.

Santhakumar V, Sutherland M, Li A, Kaghad A, Panagopoulos D, Li F, Szewczyk M, Smil D, Scholten C, Bouché L, Stellfeld T, Arrowsmith CH, Barsyte D, Vedadi M, Hartung IV, Steuber H, Britton R
ChemMedChem. 29.01.2021 . doi: 10.1002/cmdc.202100018
PMID: 33513288

2020

Identification of lysine isobutyrylation as a new histone modification mark.

Zhu Z, Han Z, Halabelian L, Yang X, Ding J, Zhang N, Ngo L, Song J, Zeng H, He M, Zhao Y, Arrowsmith CH, Luo M, Bartlett MG, Zheng YG
Nucleic Acids Res. 11.12.2020 . doi: 10.1093/nar/gkaa1176
PMID: 33313896

Epigenetics 2.0: Special Issue on Epigenetics-Call for Papers.

Conway SJ, Arimondo P, Arrowsmith C, Jin J, Luo C, Meanwell N, Young W, Georg G, Wang S
J Med Chem. 12.11.2020 63(21):12129-12130. doi: 10.1021/acs.jmedchem.0c01748
PMID: 33090784

LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium.

Zwiggelaar RT, Lindholm HT, Fosslie M, Terndrup Pedersen M, Ohta Y, Díez-Sánchez A, Martín-Alonso M, Ostrop J, Matano M, Parmar N, Kvaløy E, Spanjers RR, Nazmi K, Rye M, Drabløs F, Arrowsmith C, Arne Dahl J, Jensen KB, Sato T, Oudhoff MJ
Sci Adv. 13.09.2020 6(37):. doi: 10.1126/sciadv.abc0367
PMID: 32917713

GLUT1 inhibition blocks growth of RB1-positive triple negative breast cancer.

Wu Q, Ba-Alawi W, Deblois G, Cruickshank J, Duan S, Lima-Fernandes E, Haight J, Tonekaboni SAM, Fortier AM, Kuasne H, McKee TD, Mahmoud H, Kushida M, Cameron S, Dogan-Artun N, Chen W, Nie Y, Zhang LX, Vellanki RN, Zhou S, Prinos P, Wouters BG, Dirks PB, Done SJ, Park M, Cescon DW, Haibe-Kains B, Lupien M, Arrowsmith CH
Nat Commun. 21.08.2020 11(1):4205. doi: 10.1038/s41467-020-18020-8
PMID: 32826891

Alternative splicing and allosteric regulation modulate the chromatin binding of UHRF1.

Tauber M, Kreuz S, Lemak A, Mandal P, Yerkesh Z, Veluchamy A, Al-Gashgari B, Aljahani A, Cortés-Medina LV, Azhibek D, Fan L, Ong MS, Duan S, Houliston S, Arrowsmith CH, Fischle W
Nucleic Acids Res.. 01.07.2020 . doi: 10.1093/nar/gkaa520
PMID: 32609811

Epigenetic switch-induced viral mimicry evasion in chemotherapy resistant breast cancer.

Deblois G, Madani Tonekaboni SA, Grillo G, Martinez C, Kao YI, Tai F, Ettayebi I, Fortier AM, Savage P, Fedor AN, Liu X, Guilhamon P, Lima-Fernandes E, Murison A, Kuasne H, Ba-Alawi W, Cescon DW, Arrowsmith CH, De Carvalho DD, Haibe-Kains B, Locasale JW, Park M, Lupien M
Cancer Discov. 16.06.2020 . doi: 10.1158/2159-8290.CD-19-1493
PMID: 32546577

Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma.

Michealraj KA, Kumar SA, Kim LJY, Cavalli FMG, Przelicki D, Wojcik JB, Delaidelli A, Bajic A, Saulnier O, MacLeod G, Vellanki RN, Vladoiu MC, Guilhamon P, Ong W, Lee JJY, Jiang Y, Holgado BL, Rasnitsyn A, Malik AA, Tsai R, Richman CM, Juraschka K, Haapasalo J, Wang EY, De Antonellis P, Suzuki H, Farooq H, Balin P, Kharas K, Van Ommeren R, Sirbu O, Rastan A, Krumholtz SL, Ly M, Ahmadi M, Deblois G, Srikanthan D, Luu B, Loukides J, Wu X, Garzia L, Ramaswamy V, Kanshin E, Sánchez-Osuna M, El-Hamamy I, Coutinho FJ, Prinos P, Singh S, Donovan LK, Daniels C, Schramek D, Tyers M, Weiss S, Stein LD, Lupien M, Wouters BG, Garcia BA, Arrowsmith CH, Sorensen PH, Angers S, Jabado N, Dirks PB, Mack SC, Agnihotri S, Rich JN, Taylor MD
Cell. 20.05.2020 . doi: 10.1016/j.cell.2020.04.047
PMID: 32445698

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.

Szewczyk MM, Ishikawa Y, Organ S, Sakai N, Li F, Halabelian L, Ackloo S, Couzens AL, Eram M, Dilworth D, Fukushi H, Harding R, Dela Seña CC, Sugo T, Hayashi K, McLeod D, Zepeda C, Aman A, Sánchez-Osuna M, Bonneil E, Takagi S, Al-Awar R, Tyers M, Richard S, Takizawa M, Gingras AC, Arrowsmith CH, Vedadi M, Brown PJ, Nara H, Barsyte-Lovejoy D
Nat Commun. 14.05.2020 11(1):2396. doi: 10.1038/s41467-020-16271-z
PMID: 32409666

Discovery of a First-in-class Protein Arginine Methyltransferase 6 (PRMT6) Covalent Inhibitor.

Shen Y, Li F, Szewczyk MM, Halabelian L, Park KS, Chau I, Dong A, Zeng H, Chen H, Meng F, Barsyte-Lovejoy D, Arrowsmith CH, Brown P, Liu J, Vedadi M, Jin J
J. Med. Chem.. 05.05.2020 . doi: 10.1021/acs.jmedchem.0c00406
PMID: 32367723

Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment.

Criqui M, Qamra A, Chu TW, Sharma M, Tsao J, Henry DA, Barsyte-Lovejoy D, Arrowsmith CH, Winegarden N, Lupien M, Harrington L
Elife. 16.04.2020 9:. doi: 10.7554/eLife.47333
PMID: 32297856

2019

Discovery of a chemical probe for PRDM9.

Allali-Hassani A, Szewczyk MM, Ivanochko D, Organ SL, Bok J, Ho JSY, Gay FPH, Li F, Blazer L, Eram MS, Halabelian L, Dilworth D, Luciani GM, Lima-Fernandes E, Wu Q, Loppnau P, Palmer N, Talib SZA, Brown PJ, Schapira M, Kaldis P, O'Hagan RC, Guccione E, Barsyte-Lovejoy D, Arrowsmith CH, Sanders JM, Kattar SD, Bennett DJ, Nicholson B, Vedadi M
Nat Commun. 17.12.2019 10(1):5759. doi: 10.1038/s41467-019-13652-x
PMID: 31848333

HMCES Functions in the Alternative End-Joining Pathway of the DNA DSB Repair during Class Switch Recombination in B Cells.

Shukla V, Halabelian L, Balagere S, Samaniego-Castruita D, Feldman DE, Arrowsmith CH, Rao A, Aravind L
Mol. Cell. 15.11.2019 . doi: 10.1016/j.molcel.2019.10.031
PMID: 31806351

Discovery of small molecule antagonists of the USP5 zinc finger ubiquitin-binding domain.

Mann MK, Franzoni I, de Freitas RF, Tempel W, Houliston S, Smith L, Vedadi M, Arrowsmith CH, Harding RJ, Schapira M
J. Med. Chem.. 30.10.2019 . doi: 10.1021/acs.jmedchem.9b00988
PMID: 31663737

A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion.

Cai XC, Zhang T, Kim EJ, Jiang M, Wang K, Wang J, Chen S, Zhang N, Wu H, Li F, Dela Seña CC, Zeng H, Vivcharuk V, Niu X, Zheng W, Lee JP, Chen Y, Barsyte D, Szewczyk M, Hajian T, Ibáñez G, Dong A, Dombrovski L, Zhang Z, Deng H, Min J, Arrowsmith CH, Mazutis L, Shi L, Vedadi M, Brown PJ, Xiang J, Qin LX, Xu W, Luo M
Elife. 28.10.2019 8:. doi: 10.7554/eLife.47110
PMID: 31657716

Targeting non-bromodomain chromatin readers.

Arrowsmith CH, Schapira M
Nat. Struct. Mol. Biol.. 05.10.2019 26(10):863-869. doi: 10.1038/s41594-019-0290-2
PMID: 31582844

A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function.

Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Farham R, Cribbs A, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett JM, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schüle R, Vedadi M, Arrowsmith CH, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann UCT
J. Med. Chem.. 24.09.2019 . doi: 10.1021/acs.jmedchem.9b00562
PMID: 31550156

A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function

Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Farham R, Cribbs A, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett JM, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schüle R, Vedadi M, Arrowsmith CH, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann UCT
Journal of Medicinal Chemistry. 23.09.2019 62:9008-9025. doi: 10.1021/acs.jmedchem.9b00562
PMID: 31550156

Selective, small molecule co-factor binding site inhibition of a Su(var)3-9, Enhancer of Zeste, Trithorax (SET) domain containing lysine methyltransferase.

Taylor AP, Szewczyk MM, Kennedy S, Trush VV, Wu H, Zeng H, Dong A, de Freitas RF, Tatlock JH, Kumpf RA, Wythes M, Casimiro-Garcia A, Denny RA, Parikh MD, Li F, Barsyte-Lovejoy D, Schapira M, Vedadi M, Brown P, Arrowsmith CH, Owen DR
J. Med. Chem.. 15.08.2019 . doi: 10.1021/acs.jmedchem.9b00112
PMID: 31415173

Therapeutic Targeting of RNA Splicing Catalysis through Inhibition of Protein Arginine Methylation.

Fong JY, Pignata L, Goy PA, Kawabata KC, Lee SC, Koh CM, Musiani D, Massignani E, Kotini AG, Penson A, Wun CM, Shen Y, Schwarz M, Low DH, Rialdi A, Ki M, Wollmann H, Mzoughi S, Gay F, Thompson C, Hart T, Barbash O, Luciani GM, Szewczyk MM, Wouters BJ, Delwel R, Papapetrou EP, Barsyte-Lovejoy D, Arrowsmith CH, Minden MD, Jin J, Melnick A, Bonaldi T, Abdel-Wahab O, Guccione E
Cancer Cell. 12.08.2019 36(2):194-209.e9. doi: 10.1016/j.ccell.2019.07.003
PMID: 31408619

The MLL1 trimeric catalytic complex is a dynamic conformational ensemble stabilized by multiple weak interactions.

Kaustov L, Lemak A, Wu H, Faini M, Fan L, Fang X, Zeng H, Duan S, Allali-Hassani A, Li F, Wei Y, Vedadi M, Aebersold R, Wang Y, Houliston S, Arrowsmith CH
Nucleic Acids Res.. 10.08.2019 . doi: 10.1093/nar/gkz697
PMID: 31400120

Identification and characterization of the first fragment hits for SETDB1 Tudor domain.

Mader P, Mendoza-Sanchez R, Iqbal A, Dong A, Dobrovetsky E, Corless VB, Liew SK, Houliston SR, De Freitas RF, Smil D, Sena CCD, Kennedy S, Diaz DB, Wu H, Dombrovski L, Allali-Hassani A, Min J, Schapira M, Vedadi M, Brown PJ, Santhakumar V, Yudin AK, Arrowsmith CH
Bioorg. Med. Chem.. 12.07.2019 . doi: 10.1016/j.bmc.2019.07.020
PMID: 31327677

Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3.

Böttcher J, Dilworth D, Reiser U, Neumüller RA, Schleicher M, Petronczki M, Zeeb M, Mischerikow N, Allali-Hassani A, Szewczyk MM, Li F, Kennedy S, Vedadi M, Barsyte-Lovejoy D, Brown PJ, Huber KVM, Rogers CM, Wells CI, Fedorov O, Rumpel K, Zoephel A, Mayer M, Wunberg T, Böse D, Zahn S, Arnhof H, Berger H, Reiser C, Hörmann A, Krammer T, Corcokovic M, Sharps B, Winkler S, Häring D, Cockcroft XL, Fuchs JE, Müllauer B, Weiss-Puxbaum A, Gerstberger T, Boehmelt G, Vakoc CR, Arrowsmith CH, Pearson M, McConnell DB
Nat. Chem. Biol.. 08.07.2019 . doi: 10.1038/s41589-019-0310-x
PMID: 31285596

Target 2035: probing the human proteome.

Carter AJ, Kraemer O, Zwick M, Mueller-Fahrnow A, Arrowsmith CH, Edwards AM
Drug Discov. Today. 03.07.2019 . doi: 10.1016/j.drudis.2019.06.020
PMID: 31278990

Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1).

Xiong Y, Greschik H, Johansson C, Seifert L, Bacher J, Park KS, Babault N, Martini ML, Fagan V, Li F, Chau I, Christott T, Dilworth D, Barsyte-Lovejoy D, Vedadi M, Arrowsmith CH, Brennan PE, Fedorov O, Jung M, Farnie G, Liu J, Oppermann UCT, Schüle R, Jin J
J. Med. Chem.. 01.07.2019 . doi: 10.1021/acs.jmedchem.9b00522
PMID: 31260300

Structural basis of HMCES interactions with abasic DNA and multivalent substrate recognition.

Halabelian L, Ravichandran M, Li Y, Zeng H, Rao A, Aravind L, Arrowsmith CH
Nat. Struct. Mol. Biol.. 24.06.2019 . doi: 10.1038/s41594-019-0246-6
PMID: 31235913

Discovery of selective activators of PRC2 mutant EED-I363M.

Suh JL, Barnash KD, Abramyan TM, Li F, The J, Engelberg IA, Vedadi M, Brown PJ, Kireev DB, Arrowsmith CH, James LI, Frye SV
Sci Rep. 25.04.2019 9(1):6524. doi: 10.1038/s41598-019-43005-z
PMID: 31024026

A chemical toolbox for the study of bromodomains and epigenetic signaling.

Wu Q, Heidenreich D, Zhou S, Ackloo S, Krämer A, Nakka K, Lima-Fernandes E, Deblois G, Duan S, Vellanki RN, Li F, Vedadi M, Dilworth J, Lupien M, Brennan PE, Arrowsmith CH, Müller S, Fedorov O, Filippakopoulos P, Knapp S
Nat Commun. 23.04.2019 10(1):1915. doi: 10.1038/s41467-019-09672-2
PMID: 31015424

Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells.

Lima-Fernandes E, Murison A, da Silva Medina T, Wang Y, Ma A, Leung C, Luciani GM, Haynes J, Pollett A, Zeller C, Duan S, Kreso A, Barsyte-Lovejoy D, Wouters BG, Jin J, Carvalho DD, Lupien M, Arrowsmith CH, O'Brien CA
Nat Commun. 29.03.2019 10(1):1436. doi: 10.1038/s41467-019-09309-4
PMID: 30926792

AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation.

Wang Z, Kang L, Zhang H, Huang Y, Fang L, Li M, Brown PJ, Arrowsmith CH, Li J, Wong J
Oncogene. 20.03.2019 . doi: 10.1038/s41388-019-0790-x
PMID: 30894683

Design and characterization of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems.

Harding RJ, Loppnau P, Ackloo S, Lemak A, Hutchinson A, Hunt B, Holehouse AS, Ho JC, Fan L, Toledo-Sherman L, Seitova A, Arrowsmith CH
J. Biol. Chem.. 06.03.2019 . doi: 10.1074/jbc.RA118.007204
PMID: 30842263

A chemical biology toolbox to study protein methyltransferases and epigenetic signaling.

Scheer S, Ackloo S, Medina TS, Schapira M, Li F, Ward JA, Lewis AM, Northrop JP, Richardson PL, Kaniskan HÜ, Shen Y, Liu J, Smil D, McLeod D, Zepeda-Velazquez CA, Luo M, Jin J, Barsyte-Lovejoy D, Huber KVM, De Carvalho DD, Vedadi M, Zaph C, Brown PJ, Arrowsmith CH
Nat Commun. 03.01.2019 10(1):19. doi: 10.1038/s41467-018-07905-4
PMID: 30604761

2018

Guiding COMPASS: Dpy-30 Positions SET1/MLL Epigenetic Signaling.

Dilworth D, Arrowsmith CH
Structure. 04.12.2018 26(12):1567-1570. doi: 10.1016/j.str.2018.11.010
PMID: 30517884

Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex.

Ivanochko D, Halabelian L, Henderson E, Savitsky P, Jain H, Marcon E, Duan S, Hutchinson A, Seitova A, Barsyte-Lovejoy D, Filippakopoulos P, Greenblatt J, Lima-Fernandes E, Arrowsmith CH
Nucleic Acids Res.. 20.11.2018 . doi: 10.1093/nar/gky1192
PMID: 30462309

Direct interaction between the PRDM3 and PRDM16 tumor suppressors and the NuRD chromatin remodeling complex.

Ivanochko, D; Halabelian, L; Henderson, E; Savitsky, P; Jain, H; Marcon, E; Duan, S; Hutchinson, A; Seitova, A; Barsyte-Lovejoy, D; Filippakopoulos, P; Greenblatt, J; Lima-Fernandes, E; Arrowsmith, CH;
Nucleic Acids Research. 20.11.2018 :-. doi: 10.1093/nar/gky1192
PMID: 30462309

Characterization of inv(3) cell line OCI-AML-20 with stroma dependent CD34 expression.

Luciani GM, Xie L, Dilworth D, Tierens A, Moskovitz Y, Murison A, Szewczyk MM, Mitchell A, Lupien M, Shlush L, Dick JE, Arrowsmith CH, Barsyte-Lovejoy D, Minden MD
Exp. Hematol.. 20.10.2018 . doi: 10.1016/j.exphem.2018.10.006
PMID: 30352278

Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells.

Kagoya Y, Saijo H, Matsunaga Y, Guo T, Saso K, Anczurowski M, Wang CH, Sugata K, Murata K, Butler MO, Arrowsmith CH, Hirano N
J. Autoimmun.. 11.10.2018 . doi: 10.1016/j.jaut.2018.09.011
PMID: 30318155

MYC Interacts with the G9a Histone Methyltransferase to Drive Transcriptional Repression and Tumorigenesis.

Tu WB, Shiah YJ, Lourenco C, Mullen PJ, Dingar D, Redel C, Tamachi A, Ba-Alawi W, Aman A, Al-Awar R, Cescon DW, Haibe-Kains B, Arrowsmith CH, Raught B, Boutros PC, Penn LZ
Cancer Cell. 08.10.2018 34(4):579-595.e8. doi: 10.1016/j.ccell.2018.09.001
PMID: 30300580

The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates.

Jakobsson ME, Małecki JM, Halabelian L, Nilges BS, Pinto R, Kudithipudi S, Munk S, Davydova E, Zuhairi FR, Arrowsmith CH, Jeltsch A, Leidel SA, Olsen JV, Falnes PØ
Nat Commun. 24.08.2018 9(1):3411. doi: 10.1038/s41467-018-05646-y
PMID: 30143613

LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity.

Bonday ZQ, Cortez GS, Grogan MJ, Antonysamy S, Weichert K, Bocchinfuso WP, Li F, Kennedy S, Li B, Mader MM, Arrowsmith CH, Brown PJ, Eram MS, Szewczyk MM, Barsyte-Lovejoy D, Vedadi M, Guccione E, Campbell RM
ACS Med Chem Lett. 12.07.2018 9(7):612-617. doi: 10.1021/acsmedchemlett.8b00014
PMID: 30034588

Identification of Rpl29 as a major substrate of the lysine methyltransferase Set7/9.

Hamidi T, Singh AK, Veland N, Vemulapalli V, Chen J, Hardikar S, Bao J, Fry CJ, Yang V, Lee KA, Guo A, Arrowsmith CH, Bedford MT, Chen T
J. Biol. Chem.. 29.06.2018 . doi: 10.1074/jbc.RA118.002890
PMID: 29959229

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

Casey AE, Sinha A, Singhania R, Livingstone J, Waterhouse P, Tharmapalan P, Cruickshank J, Shehata M, Drysdale E, Fang H, Kim H, Isserlin R, Bailey S, Medina T, Deblois G, Shiah YJ, Barsyte-Lovejoy D, Hofer S, Bader G, Lupien M, Arrowsmith C, Knapp S, De Carvalho D, Berman H, Boutros PC, Kislinger T, Khokha R
J. Cell Biol.. 19.06.2018 . doi: 10.1083/jcb.201804042
PMID: 29921600

DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.

Kagoya Y, Nakatsugawa M, Saso K, Guo T, Anczurowski M, Wang CH, Butler MO, Arrowsmith CH, Hirano N
Nat Commun. 15.05.2018 9(1):1915. doi: 10.1038/s41467-018-04262-0
PMID: 29765028

Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors.

Ferreira de Freitas R, Harding RJ, Franzoni I, Ravichandran M, Mann MK, Ouyang H, Lautens M, Santhakumar V, Arrowsmith CH, Schapira M
J. Med. Chem.. 09.05.2018 . doi: 10.1021/acs.jmedchem.8b00258
PMID: 29741882

Donated chemical probes for open science.

Müller S, Ackloo S, Arrowsmith CH, Bauser M, Baryza JL, Blagg J, Böttcher J, Bountra C, Brown PJ, Bunnage ME, Carter AJ, Damerell D, Dötsch V, Drewry DH, Edwards AM, Edwards J, Elkins JM, Fischer C, Frye SV, Gollner A, Grimshaw CE, IJzerman A, Hanke T, Hartung IV, Hitchcock S, Howe T, Hughes TV, Laufer S, Li VM, Liras S, Marsden BD, Matsui H, Mathias J, O'Hagan RC, Owen DR, Pande V, Rauh D, Rosenberg SH, Roth BL, Schneider NS, Scholten C, Singh Saikatendu K, Simeonov A, Takizawa M, Tse C, Thompson PR, Treiber DK, Viana AY, Wells CI, Willson TM, Zuercher WJ, Knapp S, Mueller-Fahrnow A
Elife. 20.04.2018 7:. doi: 10.7554/eLife.34311
PMID: 29676732

Discovery of Ubiquitin Deamidases in the Pathogenic Arsenal of Legionella pneumophila.

Valleau D, Quaile AT, Cui H, Xu X, Evdokimova E, Chang C, Cuff ME, Urbanus ML, Houliston S, Arrowsmith CH, Ensminger AW, Savchenko A
Cell Rep. 10.04.2018 23(2):568-583. doi: 10.1016/j.celrep.2018.03.060
PMID: 29642013

TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma.

Nakayama K, Szewczyk MM, Dela Sena C, Wu H, Dong A, Zeng H, Li F, de Freitas RF, Eram MS, Schapira M, Baba Y, Kunitomo M, Cary DR, Tawada M, Ohashi A, Imaeda Y, Saikatendu KS, Grimshaw CE, Vedadi M, Arrowsmith CH, Barsyte-Lovejoy D, Kiba A, Tomita D, Brown PJ
Oncotarget. 06.04.2018 9(26):18480-18493. doi: 10.18632/oncotarget.24883
PMID: 29719619

Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain.

Senisterra G, Zhu HY, Luo X, Zhang H, Xun G, Lu C, Xiao W, Hajian T, Loppnau P, Chau I, Li F, Allali-Hassani A, Atadja P, Oyang C, Li E, Brown PJ, Arrowsmith CH, Zhao K, Yu Z, Vedadi M
SLAS Discov. 01.03.2018 2472555218766278. doi: 10.1177/2472555218766278
PMID: 29562800

Revealing the Protein Propionylation Activity of the Histone Acetyltransferase Males absent on the first (MOF).

Han Z, Wu H, Kim S, Yang X, Li Q, Huang H, Cai H, Bartlett MG, Dong A, Zeng H, Brown PJ, Yang X, Arrowsmith CH, Zhao Y, Zheng YG
J. Biol. Chem.. 10.01.2018 . doi: 10.1074/jbc.RA117.000529
PMID: 29321206

2017

Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3).

Kaniskan HÜ, Eram MS, Zhao K, Szewczyk MM, Yang X, Schmidt K, Luo X, Xiao S, Dai M, He F, Zang I, Lin Y, Li F, Dobrovetsky E, Smil D, Min SJ, Lin-Jones J, Schapira M, Atadja P, Li E, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Liu F, Yu Z, Vedadi M, Jin J
J. Med. Chem.. 15.12.2017 . doi: 10.1021/acs.jmedchem.7b01674
PMID: 29244490

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors.

Dahlin JL, Nelson KM, Strasser JM, Barsyte-Lovejoy D, Szewczyk MM, Organ S, Cuellar M, Singh G, Shrimp JH, Nguyen N, Meier JL, Arrowsmith CH, Brown PJ, Baell JB, Walters MA
Nat Commun. 15.11.2017 8(1):1527. doi: 10.1038/s41467-017-01657-3
PMID: 29142305

Conformational dynamics of the TTD-PHD histone reader module of UHRF1 reveals multiple histone binding states, allosteric regulation and druggability.

Houliston RS, Lemak A, Iqbal A, Ivanochko D, Duan S, Kaustov L, Ong MS, Fan L, Senisterra G, Brown PJ, Wang YX, Arrowsmith CH
J. Biol. Chem.. 26.10.2017 . doi: 10.1074/jbc.M117.799700
PMID: 29074623

WD40 repeat domain proteins: a novel target class?

Schapira M, Tyers M, Torrent M, Arrowsmith CH
Nat Rev Drug Discov. 13.10.2017 . doi: 10.1038/nrd.2017.179
PMID: 29026209

Small molecule antagonists of the interaction between the histone deacetylase 6 zinc-finger domain and ubiquitin.

Harding RJ, Ferreira de Freitas R, Collins PM, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH
J. Med. Chem.. 11.10.2017 . doi: 10.1021/acs.jmedchem.7b00933
PMID: 29019676

A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.

Mello SS, Valente LJ, Raj N, Seoane JA, Flowers BM, McClendon J, Bieging-Rolett KT, Lee J, Ivanochko D, Kozak MM, Chang DT, Longacre TA, Koong AC, Arrowsmith CH, Kim SK, Vogel H, Wood LD, Hruban RH, Curtis C, Attardi LD
Cancer Cell. 09.10.2017 32(4):460-473.e6. doi: 10.1016/j.ccell.2017.09.007
PMID: 29017057

Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy.

Global analysis of protein folding using massively parallel design, synthesis, and testing.

Rocklin GJ, Chidyausiku TM, Goreshnik I, Ford A, Houliston S, Lemak A, Carter L, Ravichandran R, Mulligan VK, Chevalier A, Arrowsmith CH, Baker D
Science. 14.07.2017 357(6347):168-175. doi: 10.1126/science.aan0693
PMID: 28706065

ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells.

Park NI, Guilhamon P, Desai K, McAdam RF, Langille E, O'Connor M, Lan X, Whetstone H, Coutinho FJ, Vanner RJ, Ling E, Prinos P, Lee L, Selvadurai H, Atwal G, Kushida M, Clarke ID, Voisin V, Cusimano MD, Bernstein M, Das S, Bader G, Arrowsmith CH, Angers S, Huang X, Lupien M, Dirks PB
Cell Stem Cell. 11.07.2017 . doi: 10.1016/j.stem.2017.06.004
PMID: 28712938

Structure-activity relationship studies of G9a-like protein (GLP) inhibitors.

Xiong Y, Li F, Babault N, Wu H, Dong A, Zeng H, Chen X, Arrowsmith CH, Brown PJ, Liu J, Vedadi M, Jin J
Bioorg. Med. Chem.. 19.06.2017 . doi: 10.1016/j.bmc.2017.06.021
PMID: 28662962

The RNF168 paralog RNF169 defines a new class of ubiquitylated-histone reader involved in the response to DNA damage.

Kitevski-LeBlanc J, Fradet-Turcotte A, Kukic P, Wilson MD, Portella G, Yuwen T, Panier S, Duan S, Canny MD, van Ingen H, Arrowsmith CH, Rubinstein JL, Vendruscolo M, Durocher D, Kay LE
Elife. 13.04.2017 6:. doi: 10.7554/eLife.23872
PMID: 28406400

Discovery of Peptidomimetic Ligands of EED as Allosteric Inhibitors of PRC2.

Barnash KD, The J, Norris-Drouin JL, Cholensky SH, Worley BM, Li F, Stuckey JI, Brown PJ, Vedadi M, Arrowsmith CH, Frye SV, James LI
ACS Comb Sci. 06.02.2017 . doi: 10.1021/acscombsci.6b00174
PMID: 28165227

Targeting human SET1/MLL family of proteins.

Vedadi M, Blazer L, Eram MS, Barsyte-Lovejoy D, Arrowsmith CH, Hajian T
Protein Sci.. 04.02.2017 . doi: 10.1002/pro.3129
PMID: 28160335

The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex.

He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J, Lima-Fernandes E, Szewczyk MM, Cheng D, Klinge KL, Li HQ, Pliushchev M, Algire MA, Maag D, Guo J, Dietrich J, Panchal SC, Petros AM, Sweis RF, Torrent M, Bigelow LJ, Senisterra G, Li F, Kennedy S, Wu Q, Osterling DJ, Lindley DJ, Gao W, Galasinski S, Barsyte-Lovejoy D, Vedadi M, Buchanan FG, Arrowsmith CH, Chiang GG, Sun C, Pappano WN
Nat. Chem. Biol.. 30.01.2017 . doi: 10.1038/nchembio.2306
PMID: 28135237

Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase.

Xiong Y, Li F, Babault N, Dong A, Zeng H, Wu H, Chen X, Arrowsmith CH, Brown PJ, Liu J, Vedadi M, Jin J
J. Med. Chem.. 30.01.2017 . doi: 10.1021/acs.jmedchem.6b01645
PMID: 28135087

The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity.

Bromberg KD, Mitchell TR, Upadhyay AK, Jakob CG, Jhala MA, Comess KM, Lasko LM, Li C, Tuzon CT, Dai Y, Li F, Eram MS, Nuber A, Soni NB, Manaves V, Algire MA, Sweis RF, Torrent M, Schotta G, Sun C, Michaelides MR, Shoemaker AR, Arrowsmith CH, Brown PJ, Santhakumar V, Martin A, Rice JC, Chiang GG, Vedadi M, Barsyte-Lovejoy D, Pappano WN
Nat. Chem. Biol.. 23.01.2017 . doi: 10.1038/nchembio.2282
PMID: 28114273

Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma.

Veschi V, Liu Z, Voss TC, Ozbun L, Gryder B, Yan C, Hu Y, Ma A, Jin J, Mazur SJ, Lam N, Souza BK, Giannini G, Hager GL, Arrowsmith CH, Khan J, Appella E, Thiele CJ
Cancer Cell. 09.01.2017 31(1):50-63. doi: 10.1016/j.ccell.2016.12.002
PMID: 28073004

2016

Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation.

Scheer S, Medina TS, Murison A, Taves MD, Antignano F, Chenery A, Soma KK, Perona-Wright G, Lupien M, Arrowsmith CH, De Carvalho DD, Zaph C
J. Leukoc. Biol.. 29.12.2016 . doi: 10.1189/jlb.3MA0716-334RR
PMID: 28034915

Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A, Norman JD, Guilhamon P, Garzia L, Agamez NR, Lu M, Chan TS, Picard D, de Antonellis P, Khuong-Quang DA, Planello AC, Zeller C, Barsyte-Lovejoy D, Lafay-Cousin L, Letourneau L, Bourgey M, Yu M, Gendoo DM, Dzamba M, Barszczyk M, Medina T, Riemenschneider AN, Morrissy AS, Ra YS, Ramaswamy V, Remke M, Dunham CP, Yip S, Ng HK, Lu JQ, Mehta V, Albrecht S, Pimentel J, Chan JA, Somers GR, Faria CC, Roque L, Fouladi M, Hoffman LM, Moore AS, Wang Y, Choi SA, Hansford JR, Catchpoole D, Birks DK, Foreman NK, Strother D, Klekner A, Bognár L, Garami M, Hauser P, Hortobágyi T, Wilson B, Hukin J, Carret AS, Van Meter TE, Hwang EI, Gajjar A, Chiou SH, Nakamura H, Toledano H, Fried I, Fults D, Wataya T, Fryer C, Eisenstat DD, Scheinemann K, Fleming AJ, Johnston DL, Michaud J, Zelcer S, Hammond R, Afzal S, Ramsay DA, Sirachainan N, Hongeng S, Larbcharoensub N, Grundy RG, Lulla RR, Fangusaro JR, Druker H, Bartels U, Grant R, Malkin D, McGlade CJ, Nicolaides T, Tihan T, Phillips J, Majewski J, Montpetit A, Bourque G, Bader GD, Reddy AT, Gillespie GY, Warmuth-Metz M, Rutkowski S, Tabori U, Lupien M, Brudno M, Schüller U, Pietsch T, Judkins AR, Hawkins CE, Bouffet E, Kim SK, Dirks PB, Taylor MD, Erdreich-Epstein A, Arrowsmith CH, De Carvalho DD, Rutka JT, Jabado N, Huang A
Cancer Cell. 12.12.2016 30(6):891-908. doi: 10.1016/j.ccell.2016.11.003
PMID: 27960086

Structure-Based Design of a Covalent Inhibitor of the SET Domain-Containing Protein 8 (SETD8) Lysine Methyltransferase.

Butler KV, Ma A, Yu W, Li F, Tempel W, Babault N, Pittella-Silva F, Shao J, Wang J, Luo M, Vedadi M, Brown PJ, Arrowsmith CH, Jin J
J. Med. Chem.. 02.11.2016 . doi: 10.1021/acs.jmedchem.6b01244
PMID: 27804297

Solution NMR structure of the HLTF HIRAN domain: a conserved module in SWI2/SNF2 DNA damage tolerance proteins.

Korzhnev DM, Neculai D, Dhe-Paganon S, Arrowsmith CH, Bezsonova I
J. Biomol. NMR. 22.10.2016 . doi: 10.1007/s10858-016-0070-9
PMID: 27771863

Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1.

Harrison JS, Cornett EM, Goldfarb D, DaRosa PA, Li ZM, Yan F, Dickson BM, Guo AH, Cantu DV, Kaustov L, Brown PJ, Arrowsmith CH, Erie DA, Major MB, Klevit RE, Krajewski K, Kuhlman B, Strahl BD, Rothbart SB
Elife. 07.09.2016 5:. doi: 10.7554/eLife.17101
PMID: 27595565

Discovery of a Potent, Selective and Cell-active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6.

Shen Y, Szewczyk MM, Eram MS, Smil D, Kaniskan HÜ, de Freitas RF, Senisterra G, Li F, Schapira M, Brown PJ, Arrowsmith CH, Barsyte-Lovejoy D, Liu J, Vedadi M, Jin J
J. Med. Chem.. 01.09.2016 . doi: 10.1021/acs.jmedchem.6b01033
PMID: 27584694

A Suite of Biochemical Assays for Screening RNA Methyltransferase BCDIN3D.

Blazer LL, Li F, Kennedy S, Zheng YG, Arrowsmith CH, Vedadi M
J Biomol Screen. 31.08.2016 . doi: 10.1177/1087057116666276
PMID: 27581605

Structure-Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors.

Yang X, Li F, Konze KD, Meslamani J, Ma A, Brown PJ, Zhou MM, Arrowsmith CH, Kaniskan HÜ, Vedadi M, Jin J
J. Med. Chem.. 28.07.2016 . doi: 10.1021/acs.jmedchem.6b00855
PMID: 27468126

Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening.

Ferreira de Freitas R, Eram MS, Smil D, Szewczyk MM, Kennedy S, Brown PJ, Santhakumar V, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M
J. Med. Chem.. 08.07.2016 . doi: 10.1021/acs.jmedchem.6b00668
PMID: 27390919

Methyltransferase inhibitors for modulation of the epigenome and beyond.

Schapira M, Arrowsmith CH
Curr Opin Chem Biol. 16.06.2016 33:81-87. doi: 10.1016/j.cbpa.2016.05.030
PMID: 27318562

Functional interdependence of BRD4 and DOT1L in MLL leukemia.

Gilan O, Lam EY, Becher I, Lugo D, Cannizzaro E, Joberty G, Ward A, Wiese M, Fong CY, Ftouni S, Tyler D, Stanley K, MacPherson L, Weng CF, Chan YC, Ghisi M, Smil D, Carpenter C, Brown P, Garton N, Blewitt ME, Bannister AJ, Kouzarides T, Huntly BJ, Johnstone RW, Drewes G, Dawson SJ, Arrowsmith CH, Grandi P, Prinjha RK, Dawson MA
Nat. Struct. Mol. Biol.. 13.06.2016 . doi: 10.1038/nsmb.3249
PMID: 27294782

An Integrative Proteomic Approach Identifies Novel Cellular SMYD2 Substrates.

Ahmed H, Duan S, Arrowsmith CH, Barsyte-Lovejoy D, Schapira M
J. Proteome Res.. 10.05.2016 . doi: 10.1021/acs.jproteome.6b00220
PMID: 27163177

PR Domain-Containing Protein 7 (PRDM7) is a Histone 3 Lysine 4 Trimethyltransferase.

Blazer LL, Lima-Fernandes E, Gibson E, Eram MS, Loppnau P, Arrowsmith CH, Schapira M, Vedadi M
J. Biol. Chem.. 29.04.2016 . doi: 10.1074/jbc.M116.721472
PMID: 27129774

Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2.

Eggert E, Hillig RC, Köhr S, Stöckigt D, Weiske J, Barak N, Mowat J, Brumby T, Christ CD, Ter Laak A, Lang T, Fernández-Montalván AE, Badock V, Weinmann H, Hartung IV, Barsyte-Lovejoy D, Szewczyk M, Kennedy S, Li F, Vedadi M, Brown PJ, Santhakumar V, Arrowsmith CH, Stellfeld T, Stresemann C
J. Med. Chem.. 13.04.2016 . doi: 10.1021/acs.jmedchem.5b01890
PMID: 27075367

SETD7 Controls Intestinal Regeneration and Tumorigenesis by Regulating Wnt/β-Catenin and Hippo/YAP Signaling.

Oudhoff MJ, Braam MJ, Freeman SA, Wong D, Rattray DG, Wang J, Antignano F, Snyder K, Refaeli I, Hughes MR, McNagny KM, Gold MR, Arrowsmith CH, Sato T, Rossi FM, Tatlock JH, Owen DR, Brown PJ, Zaph C
Dev. Cell. 04.04.2016 37(1):47-57. doi: 10.1016/j.devcel.2016.03.002
PMID: 27046831

Structure-Based Optimization of a Small Molecule Antagonist of the Interaction Between WD Repeat-Containing Protein 5 (WDR5) and Mixed-Lineage Leukemia 1 (MLL1).

Getlik M, Smil D, Zepeda-Velázquez C, Bolshan Y, Poda G, Wu H, Dong A, Kuznetsova E, Marcellus R, Senisterra G, Dombrovski L, Hajian T, Kiyota T, Schapira M, Arrowsmith CH, Brown PJ, Vedadi M, Al-Awar R
J. Med. Chem.. 09.03.2016 . doi: 10.1021/acs.jmedchem.5b01630
PMID: 26958703

Chemical Biology Approaches for Characterization of Epigenetic Regulators.

Barsyte-Lovejoy D, Szewczyk MM, Prinos P, Lima-Fernandes E, Ackloo S, Arrowsmith CH
Meth. Enzymol.. 16.02.2016 574:79-103. doi: 10.1016/bs.mie.2016.01.011
PMID: 27423858

Discovery of a Potent Class I Protein Arginine Methyltransferase Fragment Inhibitor.

Ferreira de Freitas R, Eram MS, Szewczyk MM, Steuber H, Smil D, Wu H, Li F, Senisterra G, Dong A, Brown PJ, Hitchcock M, Moosmayer D, Stegmann CM, Egner U, Arrowsmith C, Barsyte-Lovejoy D, Vedadi M, Schapira M
J. Med. Chem.. 29.01.2016 . doi: 10.1021/acs.jmedchem.5b01772
PMID: 26824386

A cellular chemical probe targeting the chromodomains of Polycomb repressive complex 1.

Stuckey JI, Dickson BM, Cheng N, Liu Y, Norris JL, Cholensky SH, Tempel W, Qin S, Huber KG, Sagum C, Black K, Li F, Huang XP, Roth BL, Baughman BM, Senisterra G, Pattenden SG, Vedadi M, Brown PJ, Bedford MT, Min J, Arrowsmith CH, James LI, Frye SV
Nat. Chem. Biol.. 25.01.2016 . doi: 10.1038/nchembio.2007
PMID: 26807715

2015

A Radioactivity-Based Assay for Screening Human m6A-RNA Methyltransferase, METTL3-METTL14 Complex, and Demethylase ALKBH5.

Li F, Kennedy S, Hajian T, Gibson E, Seitova A, Xu C, Arrowsmith CH, Vedadi M
J Biomol Screen. 23.12.2015 . doi: 10.1177/1087057115623264
PMID: 26701100

MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.

Gallo M, Coutinho FJ, Vanner RJ, Gayden T, Mack SC, Murison A, Remke M, Li R, Takayama N, Desai K, Lee L, Lan X, Park NI, Barsyte-Lovejoy D, Smil D, Sturm D, Kushida MM, Head R, Cusimano MD, Bernstein M, Clarke ID, Dick JE, Pfister SM, Rich JN, Arrowsmith CH, Taylor MD, Jabado N, Bazett-Jones DP, Lupien M, Dirks PB
Cancer Cell. 25.11.2015 . doi: 10.1016/j.ccell.2015.10.005
PMID: 26626085

A Potent, Selective and Cell-active Inhibitor of Human Type I Protein Arginine Methyltransferases.

Eram MS, Shen Y, Szewczyk M, Wu H, Senisterra G, Li F, Butler KV, Kaniskan HÜ, Speed BA, Dela Seña C, Dong A, Zeng H, Schapira M, Brown PJ, Arrowsmith CH, Barsyte-Lovejoy D, Liu J, Vedadi M, Jin J
ACS Chem. Biol.. 24.11.2015 . doi: 10.1021/acschembio.5b00839
PMID: 26598975

Design of a fluorescent ligand targeting the S-adenosylmethionine binding site of the histone methyltransferase MLL1.

Luan Y, Blazer LL, Hu H, Hajian T, Zhang J, Wu H, Houliston S, Arrowsmith CH, Vedadi M, Zheng YG
Org. Biomol. Chem.. 06.11.2015 . doi: 10.1039/c5ob01794g
PMID: 26541578

The promise and peril of chemical probes (vol 11, pg 536, 2015)

Arrowsmith, CH; Audia, JE; Austin, C; Baell, J; Bennett, J; Blagg, J; Bountra, C; Brennan, PE; Brown, PJ; Bunnage, ME; Buser-Doepner, C; Campbell, RM; Carter, AJ; Cohen, P; Copeland, RA; Cravatt, B; Dahlin, JL; Dhanak, D; Edwards, AM; Frederiksen, M; Frye, SV; Gray, N; Grimshaw, CE; Hepworth, D; Howe, T; Huber, KVM; Jin, J; Knapp, S; Kotz, JD; Kruger, RG; Lowe, D; Mader, MM; Marsden, B; Mueller-Fahrnow, A; Mueller, S; O'Hagan, RC; Overington, JP; Owen, DR; Rosenberg, SH; Ross, R; Roth, B; Schapira, M; Schreiber, SL; Shoichet, B; Sundstroem, M; Superti-Furga, G; Taunton, J; Toledo-Sherman, L; Walpole, C; Walters, MA; Willson, TM; Workman, P; Young, RN; Zuercher, WJ;
Nature Chemical Biology. 01.11.2015 11:887-887. doi: 10.1038/nchembio.1931
PMID:

Corrigendum: The promise and peril of chemical probes.

Arrowsmith, CH; Audia, JE; Austin, C; Baell, J; Bennett, J; Blagg, J; Bountra, C; Brennan, PE; Brown, PJ; Bunnage, ME; Buser-Doepner, C; Campbell, RM; Carter, AJ; Cohen, P; Copeland, RA; Cravatt, B; Dahlin, JL; Dhanak, D; Edwards, AM; Frederiksen, M; Frye, SV; Gray, N; Grimshaw, CE; Hepworth, D; Howe, T; Huber, KVM; Jin, J; Knapp, S; Kotz, JD; Kruger, RG; Lowe, D; Mader, MM; Marsden, B; Mueller-Fahrnow, A; Müller, S; O'Hagan, RC; Overington, JP; Owen, DR; Rosenberg, SH; Ross, R; Roth, B; Schapira, M; Schreiber, SL; Shoichet, B; Sundström, M; Superti-Furga, G; Taunton, J; Toledo-Sherman, L; Walpole, C; Walters, MA; Willson, TM; Workman, P; Young, RN; Zuercher, WJ;
Nature Chemical Biology. 01.11.2015 11:887-. doi: 10.1038/nchembio1115-887c
PMID: 26485080

WDR5 supports an N-Myc transcriptional complex that drives a pro-tumorigenic gene expression signature in neuroblastoma.

Sun Y, Bell JL, Carter DR, Gherardi S, Poulos RC, Milazzo G, Wong JW, Al-Awar R, Tee AE, Liu PY, Liu B, Atmadibrata B, Wong M, Trahair T, Zhao Q, Shohet JM, Haupt Y, Schulte JH, Brown PJ, Arrowsmith CH, Vedadi M, MacKenzie KL, Huttelmaier S, Perini G, Marshall GM, Braithwaite A, Liu T
Cancer Res.. 15.10.2015 . doi: 10.1158/0008-5472.CAN-15-0423
PMID: 26471359

Optimizing Production of Antigens and Fabs in the Context of Generating Recombinant Antibodies to Human Proteins.

Zhong N, Loppnau P, Seitova A, Ravichandran M, Fenner M, Jain H, Bhattacharya A, Hutchinson A, Paduch M, Lu V, Olszewski M, Kossiakoff AA, Dowdell E, Koide A, Koide S, Huang H, Nadeem V, Sidhu SS, Greenblatt JF, Marcon E, Arrowsmith CH, Edwards AM, Gräslund S
PLoS ONE. 05.10.2015 10(10):e0139695. doi: 10.1371/journal.pone.0139695
PMID: 26437229

Erratum: Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.

Grebien, F; Vedadi, M; Getlik, M; Giambruno, R; Grover, A; Avellino, R; Skucha, A; Vittori, S; Kuznetsova, E; Smil, D; Barsyte-Lovejoy, D; Li, F; Poda, G; Schapira, M; Wu, H; Dong, A; Senisterra, G; Stukalov, A; Huber, KVM; Schönegger, A; Marcellus, R; Bilban, M; Bock, C; Brown, PJ; Zuber, J; Bennett, KL; Al-Awar, R; Delwel, R; Nerlov, C; Arrowsmith, CH; Superti-Furga, G;
Nature Chemical Biology. 01.10.2015 11:815-. doi: 10.1038/nchembio1015-815b
PMID: 26379026

Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth.

Zhu J, Sammons MA, Donahue G, Dou Z, Vedadi M, Getlik M, Barsyte-Lovejoy D, Al-awar R, Katona BW, Shilatifard A, Huang J, Hua X, Arrowsmith CH, Berger SL
Nature. 10.09.2015 525(7568):206-11. doi: 10.1038/nature15251
PMID: 26331536

Probing the epigenome.

Huston A, Arrowsmith CH, Knapp S, Schapira M
Nat. Chem. Biol.. 21.07.2015 11(8):542-5. doi: 10.1038/nchembio.1871
PMID: 26196765

The promise and peril of chemical probes.

Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O'Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ
Nat. Chem. Biol.. 21.07.2015 11(8):536-41. doi: 10.1038/nchembio.1867
PMID: 26196764

Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia.

Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D, Barsyte-Lovejoy D, Li F, Poda G, Schapira M, Wu H, Dong A, Senisterra G, Stukalov A, Huber KV, Schönegger A, Marcellus R, Bilban M, Bock C, Brown PJ, Zuber J, Bennett KL, Al-Awar R, Delwel R, Nerlov C, Arrowsmith CH, Superti-Furga G
Nat. Chem. Biol.. 13.07.2015 . doi: 10.1038/nchembio.1859
PMID: 26167872

Assessment of a method to characterize antibody selectivity and specificity for use in immunoprecipitation.

Marcon E, Jain H, Bhattacharya A, Guo H, Phanse S, Pu S, Byram G, Collins BC, Dowdell E, Fenner M, Guo X, Hutchinson A, Kennedy JJ, Krastins B, Larsen B, Lin ZY, Lopez MF, Loppnau P, Miersch S, Nguyen T, Olsen JB, Paduch M, Ravichandran M, Seitova A, Vadali G, Vogelsang MS, Whiteaker JR, Zhong G, Zhong N, Zhao L, Aebersold R, Arrowsmith CH, Emili A, Frappier L, Gingras AC, Gstaiger M, Paulovich AG, Koide S, Kossiakoff AA, Sidhu SS, Wodak SJ, Gräslund S, Greenblatt JF, Edwards AM
Nat. Methods. 29.06.2015 . doi: 10.1038/nmeth.3472
PMID: 26121405

Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.

Sweis RF, Wang Z, Algire M, Arrowsmith CH, Brown PJ, Chiang GG, Guo J, Jakob CG, Kennedy S, Li F, Maag D, Shaw B, Soni NB, Vedadi M, Pappano WN
ACS Med Chem Lett. 11.06.2015 6(6):695-700. doi: 10.1021/acsmedchemlett.5b00124
PMID: 26101576

Kinetic characterization of human histone H3 lysine 36 methyltransferases, ASH1L and SETD2.

Eram MS, Kuznetsova E, Li F, Lima-Fernandes E, Kennedy S, Chau I, Arrowsmith CH, Schapira M, Vedadi M
Biochim. Biophys. Acta. 19.05.2015 . doi: 10.1016/j.bbagen.2015.05.013
PMID: 26002201

Solution-state NMR structure of the putative morphogene protein BolA (PFE0790c) from Plasmodium falciparum.

Buchko GW, Yee A, Semesi A, Myler PJ, Arrowsmith CH, Hui R
Acta Crystallogr F Struct Biol Commun. 18.04.2015 71(Pt 5):514-21. doi: 10.1107/S2053230X1402799X
PMID: 25945703

Discovery of a Dual PRMT5-PRMT7 Inhibitor.

Smil D, Eram MS, Li F, Kennedy S, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M
ACS Med Chem Lett. 09.04.2015 6(4):408-12. doi: 10.1021/ml500467h
PMID: 25893041

LLY-507, a Cell-Active, Potent and Selective Inhibitor of Protein Lysine Methyltransferase SMYD2.

Nguyen H, Allali-Hassani A, Antonysamy S, Chang S, Chen LH, Curtis C, Emtage S, Fan L, Gheyi T, Li F, Liu S, Martin JR, Mendel D, Olsen JB, Pelletier L, Shatseva T, Wu S, Zhang FF, Arrowsmith CH, Brown PJ, Campbell RM, Garcia BA, Barsyte-Lovejoy D, Mader M, Vedadi M
J. Biol. Chem.. 30.03.2015 . doi: 10.1074/jbc.M114.626861
PMID: 25825497

A Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3).

Kaniskan HÜ, Szewczyk MM, Yu Z, Eram MS, Yang X, Schmidt K, Luo X, Dai M, He F, Zang I, Lin Y, Kennedy S, Li F, Dobrovetsky E, Dong A, Smil D, Min SJ, Landon M, Lin-Jones J, Huang XP, Roth BL, Schapira M, Atadja P, Barsyte-Lovejoy D, Arrowsmith CH, Brown PJ, Zhao K, Jin J, Vedadi M
Angew. Chem. Int. Ed. Engl.. 27.02.2015 . doi: 10.1002/anie.201412154
PMID: 25728001

Preclinical target validation using patient-derived cells.

Edwards AM, Arrowsmith CH, Bountra C, Bunnage ME, Feldmann M, Knight JC, Patel DD, Prinos P, Taylor MD, Sundström M, Barker P, Barsyte D, Bengtson MH, Bell C, Bowness P, Boycott KM, Buser-Doepner C, Carpenter CL, Carr AJ, Clark K, Das AM, Dhanak D, Dirks P, Ellis J, Fantin VR, Flores C, Fon EA, Frail DE, Gileadi O, O'Hagan RC, Howe T, Isaac JT, Jabado N, Jakobsson PJ, Klareskog L, Knapp S, Lee WH, Lima-Fernandes E, Lundberg IE, Marshall J, Massirer KB, MacKenzie AE, Maruyama T, Mueller-Fahrnow A, Muthuswamy S, Nanchahal J, O'Brien C, Oppermann U, Ostermann N, Petrecca K, Pollock BG, Poupon V, Prinjha RK, Rosenberg SH, Rouleau G, Skingle M, Slutsky AS, Smith GA, Verhelle D, Widmer H, Young LT
Nat Rev Drug Discov. 20.02.2015 14(3):149-50. doi: 10.1038/nrd4565
PMID: 25722227

Identification of a Fragment-like Small Molecule Ligand for the Methyl-lysine Binding Protein, 53BP1.

Perfetti MT, Baughman BM, Dickson BM, Mu Y, Cui G, Mader P, Dong A, Norris JL, Rothbart SB, Strahl BD, Brown PJ, Janzen WP, Arrowsmith CH, Mer G, McBride KM, James LI, Frye SV
ACS Chem. Biol.. 15.01.2015 . doi: 10.1021/cb500956g
PMID: 25590533

2014

A global assessment of cancer genomic alterations in epigenetic mechanisms.

Shah MA, Denton EL, Arrowsmith CH, Lupien M, Schapira M
Epigenetics Chromatin. 04.12.2014 7(1):29. doi: 10.1186/1756-8935-7-29
PMID: 25484917

Structure and function of dioxygenases in histone demethylation and DNA/RNA demethylation.

Dong C, Zhang H, Xu C, Arrowsmith CH, Min J
IUCrJ. 01.11.2014 1(Pt 6):540-549. doi: 10.1107/S2052252514020922
PMID: 25485134

(R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells.

Barsyte-Lovejoy D, Li F, Oudhoff MJ, Tatlock JH, Dong A, Zeng H, Wu H, Freeman SA, Schapira M, Senisterra GA, Kuznetsova E, Marcellus R, Allali-Hassani A, Kennedy S, Lambert JP, Couzens AL, Aman A, Gingras AC, Al-Awar R, Fish PV, Gerstenberger BS, Roberts L, Benn CL, Grimley RL, Braam MJ, Rossi FM, Sudol M, Brown PJ, Bunnage ME, Owen DR, Zaph C, Vedadi M, Arrowsmith CH
Proc. Natl. Acad. Sci. U.S.A.. 18.08.2014 . doi: 10.1073/pnas.1407358111
PMID: 25136132

Discovery of a Selective, Substrate-competitive Inhibitor of the Lysine Methyltransferase SETD8.

Ma A, Yu W, Li F, Bleich RM, Herold JM, Butler KV, Norris JL, Korboukh V, Tripathy A, Janzen WP, Arrowsmith CH, Frye SV, Vedadi M, Brown PJ, Jin J
J. Med. Chem.. 17.07.2014 . doi: 10.1021/jm500871s
PMID: 25032507

RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.

Trimethylation of Histone H3 Lysine 36 by Human Methyltransferase PRDM9.

Eram MS, Bustos SP, Lima-Fernandes E, Siarheyeva A, Senisterra G, Hajian T, Chau I, Duan S, Wu H, Dombrovski L, Schapira M, Arrowsmith CH, Vedadi M
J. Biol. Chem.. 14.03.2014 . doi: 10.1074/jbc.M113.523183
PMID: 24634223

A Basic Post-SET Extension of NSDs Is Essential for Nucleosome Binding In Vitro.

Allali-Hassani A, Kuznetsova E, Hajian T, Wu H, Dombrovski L, Li Y, Gräslund S, Arrowsmith CH, Schapira M, Vedadi M
J Biomol Screen. 04.03.2014 . doi: 10.1177/1087057114525854
PMID: 24595546

The structure-activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface.

Camerino MA, Zhong N, Dong A, Dickson BM, James LI, Baughman BM, Norris JL, Kireev DB, Janzen WP, Arrowsmith CH, Frye SV
Medchemcomm. 28.01.2014 4(11):1501-1507. doi: 10.1039/C3MD00197K
PMID: 24466405

2013

Structure of the Catalytic Domain of EZH2 Reveals Conformational Plasticity in Cofactor and Substrate Binding Sites and Explains Oncogenic Mutations.

Wu H, Zeng H, Dong A, Li F, He H, Senisterra G, Seitova A, Duan S, Brown PJ, Vedadi M, Arrowsmith CH, Schapira M
PLoS ONE. 19.12.2013 8(12):e83737. doi: 10.1371/journal.pone.0083737
PMID: 24367611

Discovery of an in vivo Chemical Probe of the Lysine Methyltransferases G9a and GLP.

Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh VK, Huang X, Allali-Hassani A, Janzen WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J
J. Med. Chem.. 08.10.2013 . doi: 10.1021/jm401480r
PMID: 24102134

Control of the Hippo Pathway by Set7-Dependent Methylation of Yap.

Oudhoff MJ, Freeman SA, Couzens AL, Antignano F, Kuznetsova E, Min PH, Northrop JP, Lehnertz B, Barsyte-Lovejoy D, Vedadi M, Arrowsmith CH, Nishina H, Gold MR, Rossi FM, Gingras AC, Zaph C
Dev. Cell. 09.07.2013 . doi: 10.1016/j.devcel.2013.05.025
PMID: 23850191

Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation.

Rothbart SB, Dickson BM, Ong MS, Krajewski K, Houliston S, Kireev DB, Arrowsmith CH, Strahl BD.
Genes Dev.. 06.2013 27(11):1288-98. doi: 10.1101/gad.220467.113
PMID: 23752590

An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1.

Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C, Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI, Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J
ACS Chem. Biol.. 24.04.2013 . doi: 10.1021/cb400133j
PMID: 23614352

Bromo-deaza-SAH: A potent and selective DOT1L inhibitor.

Yu W, Smil D, Li F, Tempel W, Fedorov O, Nguyen KT, Bolshan Y, Al-Awar R, Knapp S, Arrowsmith CH, Vedadi M, Brown PJ, Schapira M
Bioorg. Med. Chem.. 01.04.2013 21(7):1787-94. doi: 10.1016/j.bmc.2013.01.049
PMID: 23433670

Exploiting an Allosteric Binding Site of PRMT3 Yields Potent and Selective Inhibitors.

Liu F, Li F, Ma A, Dobrovetsky E, Dong A, Gao C, Korboukh I, Liu J, Smil D, Brown PJ, Frye SV, Arrowsmith CH, Schapira M, Vedadi M, Jin J
J. Med. Chem.. 14.03.2013 56(5):2110-24. doi: 10.1021/jm3018332
PMID: 23445220

Synthesis, Optimization, and Evaluation of Novel Small Molecules as Antagonists of WDR5-MLL Interaction.

Bolshan Y, Getlik M, Kuznetsova E, Wasney GA, Hajian T, Poda G, Nguyen KT, Wu H, Dombrovski L, Dong A, Senisterra G, Schapira M, Arrowsmith CH, Brown PJ, Al-Awar R, Vedadi M, Smil D
ACS Med Chem Lett. 14.03.2013 4(3):353-7. doi: 10.1021/ml300467n
PMID: 24900672

Discovery of a chemical probe for the L3MBTL3 methyllysine reader domain.

James LI, Barsyte-Lovejoy D, Zhong N, Krichevsky L, Korboukh VK, Herold JM, Macnevin CJ, Norris JL, Sagum CA, Tempel W, Marcon E, Guo H, Gao C, Huang XP, Duan S, Emili A, Greenblatt JF, Kireev DB, Jin J, Janzen WP, Brown PJ, Bedford MT, Arrowsmith CH, Frye SV
Nat. Chem. Biol.. 06.01.2013 . doi: 10.1038/nchembio.1157
PMID: 23292653

Small-molecule inhibition of MLL activity by disruption of its interaction with WDR5.

Senisterra G, Wu H, Allali-Hassani A, Wasney GA, Barsyte-Lovejoy D, Dombrovski L, Dong A, Nguyen KT, Smil D, Bolshan Y, Hajian T, He H, Seitova A, Chau I, Li F, Poda G, Couture JF, Brown PJ, Al-Awar R, Schapira M, Arrowsmith CH, Vedadi M
Biochem. J.. 01.01.2013 449(1):151-9. doi: 10.1042/BJ20121280
PMID: 22989411

2012

Nahuoic Acid A Produced by a Streptomyces sp. Isolated From a Marine Sediment Is a Selective SAM-Competitive Inhibitor of the Histone Methyltransferase SETD8.

Williams DE, Dalisay DS, Li F, Amphlett J, Maneerat W, Chavez MA, Wang YA, Matainaho T, Yu W, Brown PJ, Arrowsmith CH, Vedadi M, Andersen RJ
Org. Lett.. 28.12.2012 . doi: 10.1021/ol303416k
PMID: 23272941

Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.

Yu W, Chory EJ, Wernimont AK, Tempel W, Scopton A, Federation A, Marineau JJ, Qi J, Barsyte-Lovejoy D, Yi J, Marcellus R, Iacob RE, Engen JR, Griffin C, Aman A, Wienholds E, Li F, Pineda J, Estiu G, Shatseva T, Hajian T, Al-Awar R, Dick JE, Vedadi M, Brown PJ, Arrowsmith CH, Bradner JE, Schapira M
Nat Commun. 18.12.2012 3:1288. doi: 10.1038/ncomms2304
PMID: 23250418

Histone recognition by human malignant brain tumor domains.

Nady N, Krichevsky L, Zhong N, Duan S, Tempel W, Amaya MF, Ravichandran M, Arrowsmith CH
J. Mol. Biol.. 09.11.2012 423(5):702-18. doi: 10.1016/j.jmb.2012.08.022
PMID: 22954662

Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation.

Rothbart SB, Krajewski K, Nady N, Tempel W, Xue S, Badeaux AI, Barsyte-Lovejoy D, Martinez JY, Bedford MT, Fuchs SM, Arrowsmith CH, Strahl BD
Nat. Struct. Mol. Biol.. 30.09.2012 19(11):1155-60. doi: 10.1038/nsmb.2391
PMID: 23022729

An allosteric inhibitor of protein arginine methyltransferase 3.

Siarheyeva A, Senisterra G, Allali-Hassani A, Dong A, Dobrovetsky E, Wasney GA, Chau I, Marcellus R, Hajian T, Liu F, Korboukh I, Smil D, Bolshan Y, Min J, Wu H, Zeng H, Loppnau P, Poda G, Griffin C, Aman A, Brown PJ, Jin J, Al-Awar R, Arrowsmith CH, Schapira M, Vedadi M
Structure. 08.08.2012 20(8):1425-35. doi: 10.1016/j.str.2012.06.001
PMID: 22795084

Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat tumbler lock.

Xu C, Jin J, Bian C, Lam R, Tian R, Weist R, You L, Nie J, Bochkarev A, Tempel W, Tan CS, Wasney GA, Vedadi M, Gish GD, Arrowsmith CH, Pawson T, Yang XJ, Min J
Sci Signal. 29.05.2012 5(226):ra39. doi: 10.1126/scisignal.2002979
PMID: 22649097

Epigenetic protein families: a new frontier for drug discovery.

Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M
Nat Rev Drug Discov. 13.04.2012 11(5):384-400. doi: 10.1038/nrd3674
PMID: 22498752

A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen.

Sheng Y, Hong JH, Doherty R, Srikumar T, Shloush J, Avvakumov GV, Walker JR, Xue S, Neculai D, Wan JW, Kim SK, Arrowsmith CH, Raught B, Dhe-Paganon S
Mol. Cell Proteomics. 10.04.2012 11(8):329-41. doi: 10.1074/mcp.O111.013706
PMID: 22496338

Histone recognition and large-scale structural analysis of the human bromodomain family.

Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Müller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S
Cell. 30.03.2012 149(1):214-31. doi: 10.1016/j.cell.2012.02.013
PMID: 22464331

Protein aggregates are recruited to aggresome by histone deacetylase 6 via unanchored ubiquitin C termini.

Ouyang H, Ali YO, Ravichandran M, Dong A, Qiu W, MacKenzie F, Dhe-Paganon S, Arrowsmith CH, Zhai RG
J. Biol. Chem.. 20.01.2012 287(4):2317-27. doi: 10.1074/jbc.M111.273730
PMID: 22069321

2011

Fluorescence-based methods for screening writers and readers of histone methyl marks.

Allali-Hassani A, Wasney GA, Siarheyeva A, Hajian T, Arrowsmith CH, Vedadi M
J Biomol Screen. 04.10.2011 17(1):71-84. doi: 10.1177/1087057111422256
PMID: 21972038

Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A.

Lemak A, Yee A, Bezsonova I, Dhe-Paganon S, Arrowsmith CH
J. Biomol. NMR. 27.09.2011 51(1-2):185-90. doi: 10.1007/s10858-011-9552-y
PMID: 21947926

Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines.

Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold JM, Chen X, Yates CM, Frye SV, Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J
J. Med. Chem.. 08.09.2011 54(17):6139-50. doi: 10.1021/jm200903z
PMID: 21780790

A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells.

Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, Labrie V, Wigle TJ, Dimaggio PA, Wasney GA, Siarheyeva A, Dong A, Tempel W, Wang SC, Chen X, Chau I, Mangano TJ, Huang XP, Simpson CD, Pattenden SG, Norris JL, Kireev DB, Tripathy A, Edwards A, Roth BL, Janzen WP, Garcia BA, Petronis A, Ellis J, Brown PJ, Frye SV, Arrowsmith CH, Jin J
Nat. Chem. Biol.. 10.07.2011 7(8):566-74. doi: 10.1038/nchembio.599
PMID: 21743462

Recognition of multivalent histone states associated with heterochromatin by UHRF1 protein.

Nady N, Lemak A, Walker JR, Avvakumov GV, Kareta MS, Achour M, Xue S, Duan S, Allali-Hassani A, Zuo X, Wang YX, Bronner C, Chédin F, Arrowsmith CH, Dhe-Paganon S
J. Biol. Chem.. 08.07.2011 286(27):24300-11. doi: 10.1074/jbc.M111.234104
PMID: 21489993

Small-molecule ligands of methyl-lysine binding proteins.

Herold JM, Wigle TJ, Norris JL, Lam R, Korboukh VK, Gao C, Ingerman LA, Kireev DB, Senisterra G, Vedadi M, Tripathy A, Brown PJ, Arrowsmith CH, Jin J, Janzen WP, Frye SV
J. Med. Chem.. 14.04.2011 54(7):2504-11. doi: 10.1021/jm200045v
PMID: 21417280

Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53.

Liao JC, Lam R, Brazda V, Duan S, Ravichandran M, Ma J, Xiao T, Tempel W, Zuo X, Wang YX, Chirgadze NY, Arrowsmith CH
Structure. 09.03.2011 19(3):418-29. doi: 10.1016/j.str.2010.12.015
PMID: 21397192

Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation.

Yap DB, Chu J, Berg T, Schapira M, Cheng SW, Moradian A, Morin RD, Mungall AJ, Meissner B, Boyle M, Marquez VE, Marra MA, Gascoyne RD, Humphries RK, Arrowsmith CH, Morin GB, Aparicio SA
Blood. 24.02.2011 117(8):2451-9. doi: 10.1182/blood-2010-11-321208
PMID: 21190999

Structural and functional comparison of the RING domains of two p53 E3 ligases, Mdm2 and Pirh2.

Shloush J, Vlassov JE, Engson I, Duan S, Saridakis V, Dhe-Paganon S, Raught B, Sheng Y, Arrowsmith CH
J. Biol. Chem.. 11.02.2011 286(6):4796-808. doi: 10.1074/jbc.M110.157669
PMID: 21084285

Recognition and specificity determinants of the human cbx chromodomains.

Kaustov L, Ouyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney GA, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH
J. Biol. Chem.. 07.01.2011 286(1):521-9. doi: 10.1074/jbc.M110.191411
PMID: 21047797

2010

Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity.

Ko S, Kang GB, Song SM, Lee JG, Shin DY, Yun JH, Sheng Y, Cheong C, Jeon YH, Jung YK, Arrowsmith CH, Avvakumov GV, Dhe-Paganon S, Yoo YJ, Eom SH, Lee W
J. Biol. Chem.. 12.11.2010 285(46):36070-80. doi: 10.1074/jbc.M110.145219
PMID: 20826778

Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.

Liu F, Chen X, Allali-Hassani A, Quinn AM, Wigle TJ, Wasney GA, Dong A, Senisterra G, Chau I, Siarheyeva A, Norris JL, Kireev DB, Jadhav A, Herold JM, Janzen WP, Arrowsmith CH, Frye SV, Brown PJ, Simeonov A, Vedadi M, Jin J
J. Med. Chem.. 12.08.2010 53(15):5844-57. doi: 10.1021/jm100478y
PMID: 20614940

Biophysical characterization of recombinant proteins: a key to higher structural genomics success.

Vedadi M, Arrowsmith CH, Allali-Hassani A, Senisterra G, Wasney GA
J. Struct. Biol.. 11.05.2010 172(1):107-19. doi: 10.1016/j.jsb.2010.05.005
PMID: 20466062

Pharmacophore screening of the protein data bank for specific binding site chemistry.

Campagna-Slater V, Arrowsmith AG, Zhao Y, Schapira M
J Chem Inf Model. 22.03.2010 50(3):358-67. doi: 10.1021/ci900427b
PMID: 20112952

Structural biology of human H3K9 methyltransferases.

Wu H, Min J, Lunin VV, Antoshenko T, Dombrovski L, Zeng H, Allali-Hassani A, Campagna-Slater V, Vedadi M, Arrowsmith CH, Plotnikov AN, Schapira M
PLoS ONE. 11.01.2010 5(1):e8570. doi: 10.1371/journal.pone.0008570
PMID: 20084102

2009

Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a.

Liu F, Chen X, Allali-Hassani A, Quinn AM, Wasney GA, Dong A, Barsyte D, Kozieradzki I, Senisterra G, Chau I, Siarheyeva A, Kireev DB, Jadhav A, Herold JM, Frye SV, Arrowsmith CH, Brown PJ, Simeonov A, Vedadi M, Jin J
J. Med. Chem.. 24.12.2009 52(24):7950-3. doi: 10.1021/jm901543m
PMID: 19891491

Screening for inhibitors of low-affinity epigenetic peptide-protein interactions: an AlphaScreen-based assay for antagonists of methyl-lysine binding proteins.

Wigle TJ, Herold JM, Senisterra GA, Vedadi M, Kireev DB, Arrowsmith CH, Frye SV, Janzen WP
J Biomol Screen. 11.12.2009 15(1):62-71. doi: 10.1177/1087057109352902
PMID: 20008125

A survey of proteins encoded by non-synonymous single nucleotide polymorphisms reveals a significant fraction with altered stability and activity.

Allali-Hassani A, Wasney GA, Chau I, Hong BS, Senisterra G, Loppnau P, Shi Z, Moult J, Edwards AM, Arrowsmith CH, Park HW, Schapira M, Vedadi M
Biochem. J.. 15.11.2009 424(1):15-26. doi: 10.1042/BJ20090723
PMID: 19702579

Ring1B contains a ubiquitin-like docking module for interaction with Cbx proteins.

Bezsonova I, Walker JR, Bacik JP, Duan S, Dhe-Paganon S, Arrowsmith CH
Biochemistry. 10.11.2009 48(44):10542-8. doi: 10.1021/bi901131u
PMID: 19791798

Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2.

Guo Y, Nady N, Qi C, Allali-Hassani A, Zhu H, Pan P, Adams-Cioaba MA, Amaya MF, Dong A, Vedadi M, Schapira M, Read RJ, Arrowsmith CH, Min J
Nucleic Acids Res.. 20.02.2009 37(7):2204-10. doi: 10.1093/nar/gkp086
PMID: 19233876

2008

Molecular basis of Pirh2-mediated p53 ubiquitylation

Sheng Y, Laister RC, Lemak A, Wu B, Tai E, Duan S, Lukin J, Sunnerhagen M, Srisailam S, Karra M, Benchimol S, Arrowsmith CH
Nat Struct Mol Biol.. 12.2008 15(12):1334-42. doi: 10.1038/nsmb.1521
PMID: 19043414

Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1.

Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, Arrowsmith CH, Dhe-Paganon S
Nature. 09.10.2008 455(7214):822-5. doi: 10.1038/nature07273
PMID: 18772889

A SPOT on the chromatin landscape? Histone peptide arrays as a tool for epigenetic research.

Nady N, Min J, Kareta MS, Chédin F, Arrowsmith CH
Trends Biochem. Sci.. 04.06.2008 33(7):305-13. doi: 10.1016/j.tibs.2008.04.014
PMID: 18538573

Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.

Schuetz A, Min J, Allali-Hassani A, Schapira M, Shuen M, Loppnau P, Mazitschek R, Kwiatkowski NP, Lewis TA, Maglathin RL, McLean TH, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH
J. Biol. Chem.. 25.04.2008 283(17):11355-63. doi: 10.1074/jbc.M707362200
PMID: 18285338

Structural genomics and drug discovery: all in the family.

Weigelt J, McBroom-Cerajewski LD, Schapira M, Zhao Y, Arrowsmith CH, Arrowmsmith CH
Curr Opin Chem Biol. 07.03.2008 12(1):32-9. doi: 10.1016/j.cbpa.2008.01.045
PMID: 18282486

Protein production and purification.

Gräslund S, Nordlund P, Weigelt J, Hallberg BM, Bray J, Gileadi O, Knapp S, Oppermann U, Arrowsmith C, Hui R, Ming J, dhe-Paganon S, Park HW, Savchenko A, Yee A, Edwards A, Vincentelli R, Cambillau C, Kim R, Kim SH, Rao Z, Shi Y, Terwilliger TC, Kim CY, Hung LW, Waldo GS, Peleg Y, Albeck S, Unger T, Dym O, Prilusky J, Sussman JL, Stevens RC, Lesley SA, Wilson IA, Joachimiak A, Collart F, Dementieva I, Donnelly MI, Eschenfeldt WH, Kim Y, Stols L, Wu R, Zhou M, Burley SK, Emtage JS, Sauder JM, Thompson D, Bain K, Luz J, Gheyi T, Zhang F, Atwell S, Almo SC, Bonanno JB, Fiser A, Swaminathan S, Studier FW, Chance MR, Sali A, Acton TB, Xiao R, Zhao L, Ma LC, Hunt JF, Tong L, Cunningham K, Inouye M, Anderson S, Janjua H, Shastry R, Ho CK, Wang D, Wang H, Jiang M, Montelione GT, Stuart DI, Owens RJ, Daenke S, Schütz A, Heinemann U, Yokoyama S, Büssow K, Gunsalus KC
Nat. Methods. 01.02.2008 5(2):135-46. doi: 10.1038/nmeth.f.202
PMID: 18235434

2007

In situ proteolysis for protein crystallization and structure determination.

Dong A, Xu X, Edwards AM; Midwest Center for Structural Genomics; Structural Genomics Consortium, Chang C, Chruszcz M, Cuff M, Cymborowski M, Di Leo R, Egorova O, Evdokimova E, Filippova E, Gu J, Guthrie J, Ignatchenko A, Joachimiak A, Klostermann N, Kim Y, Korniyenko Y, Minor W, Que Q, Savchenko A, Skarina T, Tan K, Yakunin A, Yee A, Yim V, Zhang R, Zheng H, Akutsu M, Arrowsmith C, Avvakumov GV, Bochkarev A, Dahlgren LG, Dhe-Paganon S, Dimov S, Dombrovski L, Finerty P Jr, Flodin S, Flores A, Gräslund S, Hammerström M, Herman MD, Hong BS, Hui R, Johansson I, Liu Y, Nilsson M, Nedyalkova L, Nordlund P, Nyman T, Min J, Ouyang H, Park HW, Qi C, Rabeh W, Shen L, Shen Y, Sukumard D, Tempel W, Tong Y, Tresagues L, Vedadi M, Walker JR, Weigelt J, Welin M, Wu H, Xiao T, Zeng H, Zhu H.
Nat Methods. 01.12.2007 4(12):1019-21. doi:
PMID: 17982461

L3MBTL1 recognition of mono- and dimethylated histones.

Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y, MacKenzie F, Vedadi M, Arrowsmith CH
Nat. Struct. Mol. Biol.. 18.11.2007 14(12):1229-30. doi: 10.1038/nsmb1340
PMID: 18026117

In situ proteolysis for protein crystallization and structure determination.

Dong A, Xu X, Edwards AM, Chang C, Chruszcz M, Cuff M, Cymborowski M, Di Leo R, Egorova O, Evdokimova E, Filippova E, Gu J, Guthrie J, Ignatchenko A, Joachimiak A, Klostermann N, Kim Y, Korniyenko Y, Minor W, Que Q, Savchenko A, Skarina T, Tan K, Yakunin A, Yee A, Yim V, Zhang R, Zheng H, Akutsu M, Arrowsmith C, Avvakumov GV, Bochkarev A, Dahlgren LG, Dhe-Paganon S, Dimov S, Dombrovski L, Finerty P, Flodin S, Flores A, Gräslund S, Hammerström M, Herman MD, Hong BS, Hui R, Johansson I, Liu Y, Nilsson M, Nedyalkova L, Nordlund P, Nyman T, Min J, Ouyang H, Park HW, Qi C, Rabeh W, Shen L, Shen Y, Sukumard D, Tempel W, Tong Y, Tresagues L, Vedadi M, Walker JR, Weigelt J, Welin M, Wu H, Xiao T, Zeng H, Zhu H
Nat. Methods. 04.11.2007 4(12):1019-21. doi: 10.1038/nmeth1118
PMID: 17982461

Structural and chemical profiling of the human cytosolic sulfotransferases.

Allali-Hassani A, Pan PW, Dombrovski L, Najmanovich R, Tempel W, Dong A, Loppnau P, Martin F, Thornton J, Thonton J, Edwards AM, Bochkarev A, Plotnikov AN, Vedadi M, Arrowsmith CH
PLoS Biol.. 12.04.2007 5(5):e97. doi: 10.1371/journal.pbio.0050097
PMID: 17425406

Analysis of binding site similarity, small-molecule similarity and experimental binding profiles in the human cytosolic sulfotransferase family.

Najmanovich RJ, Allali-Hassani A, Morris RJ, Dombrovsky L, Pan PW, Vedadi M, Plotnikov AN, Edwards A, Arrowsmith C, Thornton JM
Bioinformatics. 15.01.2007 23(2):e104-9. doi: 10.1093/bioinformatics/btl292
PMID: 17237076

2006

Genome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organisms.

Vedadi M, Lew J, Artz J, Amani M, Zhao Y, Dong A, Wasney GA, Gao M, Hills T, Brokx S, Qiu W, Sharma S, Diassiti A, Alam Z, Melone M, Mulichak A, Wernimont A, Bray J, Loppnau P, Plotnikova O, Newberry K, Sundararajan E, Houston S, Walker J, Tempel W, Bochkarev A, Kozieradzki I, Edwards A, Arrowsmith C, Roos D, Kain K, Hui R
Mol. Biochem. Parasitol.. 13.11.2006 151(1):100-10. doi: 10.1016/j.molbiopara.2006.10.011
PMID: 17125854

Chemical screening methods to identify ligands that promote protein stability, protein crystallization, and structure determination.

Vedadi M, Niesen FH, Allali-Hassani A, Fedorov OY, Finerty PJ, Wasney GA, Yeung R, Arrowsmith C, Ball LJ, Berglund H, Hui R, Marsden BD, Nordlund P, Sundstrom M, Weigelt J, Edwards AM
Proc. Natl. Acad. Sci. U.S.A.. 24.10.2006 103(43):15835-40. doi: 10.1073/pnas.0605224103
PMID: 17035505

Structural basis for molecular recognition and presentation of histone H3 by WDR5.

Schuetz A, Allali-Hassani A, Martín F, Loppnau P, Vedadi M, Bochkarev A, Plotnikov AN, Arrowsmith CH, Min J
EMBO J.. 20.09.2006 25(18):4245-52. doi: 10.1038/sj.emboj.7601316
PMID: 16946699

Molecular recognition of p53 and MDM2 by USP7/HAUSP

Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, Frappier L.
Nat Struct Mol Biol.. 03.2006 13(3):285-91. doi:
PMID: 16474402