Cheryl H. Arrowsmith

Chief Scientist

University of Toronto

Cheryl is the Chief Scientist for the SGC Toronto laboratories, Professor of Medical Biophysics at the University of Toronto, Senior Scientist at the Ontario Cancer Institute/Princess Margaret Cancer Center, and Canada Research Chair in Structural Genomics. 

Cheryl obtained her PhD in chemistry at the University of Toronto and did postdoctoral training at Stanford in protein structural biology using NMR spectroscopy. Cheryl has studied the structure and function of transcription regulatory proteins such as the tumor suppressor, p53, and its regulators.  A long time collaborator of Aled Edwards (SGC Director), the pair teamed up in the late 1990’s to develop structural biology methods for genome-scale research -  a concept that grew into the field of Structural Genomics.

Her current research interests focus on structural and chemical biology of epigenetic signaling, especially methylation dependent chromatin signaling. She coordinates the SGC’s structure-guided epigenetic chemical probe program and collaborates with numerous groups to use chemical probes to better understand epigenetic vulnerabilities in cancer and inflammatory bowel disease, and how to harness this knowledge for new therapies.

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.. 2013 27(11):1288-98. doi: 10.1101/gad.220467.113
PMID: 23752590

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

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

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.. 2011 286(27):24300-11. doi: 10.1074/jbc.M111.234104
PMID: 21489993

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.. 2011 286(1):521-9. doi: 10.1074/jbc.M110.191411
PMID: 21047797

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. 2008 455(7214):822-5. doi: 10.1038/nature07273
PMID: 18772889

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

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.. 2008 283(17):11355-63. doi: 10.1074/jbc.M707362200
PMID: 18285338

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.. 2006 13(3):285-91. doi:
PMID: 16474402

2017

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

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, 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; 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:
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

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.
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.. 06.07.2014 . doi: 10.1038/nsmb.2853
PMID: 24997600

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

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

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