Daria
Dalia Barsyte-Lovejoy

Principal Investigator

University of Toronto

Dr. Dalia Barsyte-Lovejoy, PhD is an Assistant Professor at the Department of Pharmacology and Toxicology, UofT, and Principal Investigator at the SGC-Toronto working to understand fundamental regulatory mechanisms of epigenetic proteins and their pharmacological modulation in cancer. Her research focuses on chemical probe discovery, disease mechanisms, and therapeutic target validation. Her research at the SGC-Toronto has played an instrumental role in the cellular characterization of chemical probes and functional target investigations. Importantly, her chemical probe work provided 25 extensively characterized compounds that have helped shape the emerging field of epigenetics and enabled over 50 collaborative projects that are uncovering new epigenetic mechanisms in cancer and its treatment.

Research Areas

We are interested in understanding the mechanism of epigenetic regulators that control cell growth, differentiation, carcinogenesis and adaptation. Through use of the chemical probes to target the epigenetic regulators we are investigating the cellular functions of these proteins and their potential to become therapeutic targets in such diseases as cancer. Our work focuses on protein lysine and arginine methyltransferases involved in transcription, genome stability, RNA metabolism and variety of cell processes determined by the substrates of these cellular enzymes. The PRMT, arginine methyltransferase, family has especially wide scope of substrates ranging from histones to signaling molecules, enzymes and structural proteins. Through multidisciplinary research that includes cell and chemical biology, protein structural biology and many collaborative studies with colleagues across industry and academia, the SGC chemical probes project has generated several probes for various PRMTs. We are currently using the chemical probes to explore the cellular pathways that are controlled by PRMT enzymes in especially poor prognosis acute myeloid leukemia patient cells. The long term patient leukemia cell cultures developed in our group enable us to investigate the cancer cell growth, drug resistance and self-renewal capacity.

 

Epigenetics and chromatin architecture regulators

 

Epigenetics and chromatin architecture regulators

Epigenetics is about how the DNA code is regulated. Proteins that bind/modify DNA and histones play essential roles in cell identity determination, transcription, and genome maintenance. They are often responsible for diseases such as cancer or uncontrolled inflammation.

We are studying how epigenetic proteins regulate normal cell processes and how these are subverted in disease. 

Chemical probes as tools for cancer target discovery

Chemical probes as tools for cancer target discovery

To study epigenetic modifier proteins, we need genetic and pharmacological tools. Chemical probe compounds that potently and selectively inhibit or degrade the target proteins in cells provide tools for modulating activating/repressing histone marks and other cellular signaling pathways. By discovering and using chemical probes, we expand our understanding of the protein function and its therapeutic utility to establish a biological rationale in cancer therapy. 

 

For more information please see Group Research and Members tab above.


Link to Open Lab notebooks that features science community posts on our various projects https://openlabnotebooks.org/

 

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

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.. 2017 . doi: 10.1038/nchembio.2282
PMID: 28114273

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.. 2016 . doi: 10.1021/acs.jmedchem.6b01033
PMID: 27584694

An Integrative Proteomic Approach Identifies Novel Cellular SMYD2 Substrates.
Ahmed H, Duan S, Arrowsmith CH, Barsyte-Lovejoy D, Schapira M
J. Proteome Res.. 2016 . doi: 10.1021/acs.jproteome.6b00220
PMID: 27163177

Chemical Biology Approaches for Characterization of Epigenetic Regulators.
Barsyte-Lovejoy D, Szewczyk MM, Prinos P, Lima-Fernandes E, Ackloo S, Arrowsmith CH
Meth. Enzymol.. 2016 574:79-103. doi: 10.1016/bs.mie.2016.01.011
PMID: 27423858

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.. 2015 . doi: 10.1021/acschembio.5b00839
PMID: 26598975

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

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

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.. 2015 . doi: 10.1002/anie.201412154
PMID: 25728001

(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.. 2014 . doi: 10.1073/pnas.1407358111
PMID: 25136132

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.. 2013 . doi: 10.1021/cb400133j
PMID: 23614352

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

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.. 2013 449(1):151-9. doi: 10.1042/BJ20121280
PMID: 22989411

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

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

Protein arginine methylation: from enigmatic functions to therapeutic targeting.
Wu Q, Schapira M, Arrowsmith CH, Barsyte-Lovejoy D
Nat Rev Drug Discov. 2021 . doi: 10.1038/s41573-021-00159-8
PMID: 33742187

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

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. 2020 11(1):2396. doi: 10.1038/s41467-020-16271-z
PMID: 32409666

2023

The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition.
Kimani SW, Perveen S, Szewezyk M, Zeng H, Dong A, Li F, Ghiabi P, Li Y, Chau I, Arrowsmith CH, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Halabelian L
Commun Biol. 16.12.2023 6(1):1272. doi: 10.1038/s42003-023-05655-8
PMID: 38104184

Development of HC-258, a Covalent Acrylamide TEAD Inhibitor That Reduces Gene Expression and Cell Migration.
Fnaiche A, Chan HC, Paquin A, González Suárez N, Vu V, Li F, Allali-Hassani A, Cao MA, Szewczyk MM, Bolotokova A, Allemand F, Gelin M, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Guichou JF, Annabi B, Gagnon A
ACS Med Chem Lett. 14.12.2023 14(12):1746-1753. doi: 10.1021/acsmedchemlett.3c00386
PMID: 38116405

Epigenetic vulnerabilities of leukemia harboring inactivating EZH2 mutations.
Alqazzaz MA, Luciani GM, Vu V, Machado RAC, Szewczyk MM, Adamson EC, Cheon S, Li F, Arrowsmith CH, Minden MD, Barsyte-Lovejoy D
Exp Hematol. 10.12.2023 104135. doi: 10.1016/j.exphem.2023.11.009
PMID: 38072134

Development of LM-41 and AF-2112, two flufenamic acid-derived TEAD inhibitors obtained through the replacement of the trifluoromethyl group by aryl rings.
Fnaiche A, Mélin L, Suárez NG, Paquin A, Vu V, Li F, Allali-Hassani A, Bolotokova A, Allemand F, Gelin M, Cotelle P, Woo S, LaPlante SR, Barsyte-Lovejoy D, Santhakumar V, Vedadi M, Guichou JF, Annabi B, Gagnon A
Bioorg Med Chem Lett. 26.09.2023 129488. doi: 10.1016/j.bmcl.2023.129488
PMID: 37770003

HiBiT Cellular Thermal Shift Assay (HiBiT CETSA).
Ramachandran S, Szewczyk M, Barghout SH, Ciulli A, Barsyte-Lovejoy D, Vu V
Methods Mol Biol. 10.08.2023 2706:149-165. doi: 10.1007/978-1-0716-3397-7_11
PMID: 37558947

Discovery and Characterization of a Chemical Probe Targeting the Zinc-Finger Ubiquitin-Binding Domain of HDAC6.
Harding RJ, Franzoni I, Mann MK, Szewczyk MM, Mirabi B, Ferreira de Freitas R, Owens DDG, Ackloo S, Scheremetjew A, Juarez-Ornelas KA, Sanichar R, Baker RJ, Dank C, Brown PJ, Barsyte-Lovejoy D, Santhakumar V, Schapira M, Lautens M, Arrowsmith CH
J Med Chem. 27.07.2023 . doi: 10.1021/acs.jmedchem.3c00314
PMID: 37499118

Discovery of a Potent and Selective Targeted NSD2 Degrader for the Reduction of H3K36me2.
Hanley RP, Nie DY, Tabor JR, Li F, Sobh A, Xu C, Barker NK, Dilworth D, Hajian T, Gibson E, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Herring LE, Wang GG, Licht JD, Vedadi M, Arrowsmith CH, James LI
J Am Chem Soc. 28.03.2023 . doi: 10.1021/jacs.3c01421
PMID: 36976643

Discovery of Nanomolar DCAF1 Small Molecule Ligands.
Li ASM, Kimani S, Wilson B, Noureldin M, González-Álvarez H, Mamai A, Hoffer L, Guilinger JP, Zhang Y, von Rechenberg M, Disch JS, Mulhern CJ, Slakman BL, Cuozzo JW, Dong A, Poda G, Mohammed M, Saraon P, Mittal M, Modh P, Rathod V, Patel B, Ackloo S, Santhakumar V, Szewczyk MM, Barsyte-Lovejoy D, Arrowsmith CH, Marcellus R, Guié MA, Keefe AD, Brown PJ, Halabelian L, Al-Awar R, Vedadi M
J Med Chem. 22.03.2023 . doi: 10.1021/acs.jmedchem.2c02132
PMID: 36948210

Reference compounds for characterizing cellular injury in high-content cellular morphology assays.
Dahlin JL, Hua BK, Zucconi BE, Nelson SD, Singh S, Carpenter AE, Shrimp JH, Lima-Fernandes E, Wawer MJ, Chung LPW, Agrawal A, O'Reilly M, Barsyte-Lovejoy D, Szewczyk M, Li F, Lak P, Cuellar M, Cole PA, Meier JL, Thomas T, Baell JB, Brown PJ, Walters MA, Clemons PA, Schreiber SL, Wagner BK
Nat Commun. 13.03.2023 14(1):1364. doi: 10.1038/s41467-023-36829-x
PMID: 36914634

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

Studying Protein Arginine Methylation: Approaches and Methods.
Barsyte-Lovejoy D
J Vis Exp. 20.01.2023 . doi: 10.3791/64821
PMID: 37602846

2022

Skeletal muscle metabolism and contraction performance regulation by teneurin C-terminal-associated peptide-1.
Hogg DW, Reid AL, Dodsworth TL, Chen Y, Reid RM, Xu M, Husic M, Biga PR, Slee A, Buck LT, Barsyte-Lovejoy D, Locke M, Lovejoy DA
Front Physiol. 17.12.2022 13:1031264. doi: 10.3389/fphys.2022.1031264
PMID: 36523555

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

Chemical biology and pharmacology of histone lysine methylation inhibitors.
Barghout SH, Machado RAC, Barsyte-Lovejoy D
Biochim Biophys Acta Gene Regul Mech. 23.06.2022 194840. doi: 10.1016/j.bbagrm.2022.194840
PMID: 35753676

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

PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade.
Srour N, Villarreal OD, Hardikar S, Yu Z, Preston S, Miller WH, Szewczyk MM, Barsyte-Lovejoy D, Xu H, Chen T, Del Rincón SV, Richard S
Cell Rep. 29.03.2022 38(13):110582. doi: 10.1016/j.celrep.2022.110582
PMID: 35354055

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

2021

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

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells.
Szewczyk MM, Vu V, Barsyte-Lovejoy D
J Vis Exp. 07.08.2021 . doi: 10.3791/62418
PMID: 34424246

Structure and Function of Protein Arginine Methyltransferase PRMT7.
Halabelian L, Barsyte-Lovejoy D
Life (Basel). 30.07.2021 11(8):. doi: 10.3390/life11080768
PMID: 34440512

Development of LM98, a Small-Molecule TEAD Inhibitor Derived from Flufenamic Acid.
Gagnon A, Mélin L, Abdullayev S, Fnaiche A, Vu V, Gonzalez Suarez N, Zeng H, Szewczyk M, Li F, Sinisterra G, Allali-Hassani A, Chau I, Dong A, Woo S, Annabi B, Halabelian L, LaPlante S, Vedadi M, Barsyte-Lovejoy D, Santhakumar V
ChemMedChem. 23.06.2021 . doi: 10.1002/cmdc.202100432
PMID: 34164919

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

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

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

2020

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

Synthetic Peptides as Therapeutic Agents: Lessons Learned From Evolutionary Ancient Peptides and Their Transit Across Blood-Brain Barriers.
Lovejoy DA, Hogg DW, Dodsworth TL, Jurado FR, Read CC, D'Aquila AL, Barsyte-Lovejoy D
Front Endocrinol (Lausanne). 30.11.2019 10:730. doi: 10.3389/fendo.2019.00730
PMID: 31781029

SETD7 at the heart of chromatin factor interplay.
Barsyte-Lovejoy D
Stem Cell Investig. 29.09.2019 6:20. doi: 10.21037/sci.2019.06.01
PMID: 31559307

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

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.
Sin-Chan P, Mumal I, Suwal T, Ho B, Fan X, Singh I, Du Y, Lu M, Patel N, Torchia J, Popovski D, Fouladi M, Guilhamon P, Hansford JR, Leary S, Hoffman LM, Mulcahy Levy JM, Lassaletta A, Solano-Paez P, Rivas E, Reddy A, Gillespie GY, Gupta N, Van Meter TE, Nakamura H, Wong TT, Ra YS, Kim SK, Massimi L, Grundy RG, Fangusaro J, Johnston D, Chan J, Lafay-Cousin L, Hwang EI, Wang Y, Catchpoole D, Michaud J, Ellezam B, Ramanujachar R, Lindsay H, Taylor MD, Hawkins CE, Bouffet E, Jabado N, Singh SK, Kleinman CL, Barsyte-Lovejoy D, Li XN, Dirks PB, Lin CY, Mack SC, Rich JN, Huang A
Cancer Cell. 08.07.2019 36(1):51-67.e7. doi: 10.1016/j.ccell.2019.06.002
PMID: 31287992

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

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

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

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

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

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

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

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

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

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

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

2016

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

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

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

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

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

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

2015

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

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

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

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

2014

(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

A Chemical Tool for In Vitro and In Vivo Precipitation of Lysine Methyltransferase G9a.
Konze KD, Pattenden SG, Liu F, Barsyte-Lovejoy D, Li F, Simon JM, Davis IJ, Vedadi M, Jin J
ChemMedChem. 17.01.2014 . doi: 10.1002/cmdc.201300450
PMID: 24443078

2013

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

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

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

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

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

C-terminal processing of the teneurin proteins: Independent actions of a teneurin C-terminal associated peptide in hippocampal cells.
Chand D, Casatti CA, de Lannoy L, Song L, Kollara A, Barsyte-Lovejoy D, Brown TJ, Lovejoy DA
Mol. Cell. Neurosci.. 28.09.2012 52:38-50. doi: 10.1016/j.mcn.2012.09.006
PMID: 23026563

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

2011

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

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