Peter J. Brown

Principal Investigator

University of Toronto
+1 416.978.7408

Peter received his Ph.D. in Organic Chemistry from the University of Sheffield and performed postdoctoral research at Indiana University with Philip Magnus culminating in the total synthesis of (-)-Pleiomutine, a bis-indole alkaloid.  Prior to joining the SGC in 2009, Peter spent nineteen years at GlaxoSmithKline in various roles, most recently Section Head, Medicinal Chemistry, and was focused on the early Hit-ID phase of Drug Discovery and finding tool compounds for the Nuclear Receptor family of proteins.  Peter’s research interests include using HTS, target-specific arrays, and fragment-based methods to discover probes for epigenetic targets.

Research Areas

Discovery of potent, selective, cell-active chemical probes for epigenetic targets using innovative methods. Identification of new templates for optimization by the use of fragment screening and focussed library design. The goal of the Epigenetic Chemical Probes group is to identify small molecules which interact with epigenetic targets with the folowing properties: - IC50 (inhibitors) or Kd (antagonists) < 100nM. - >30-fold selectivity over targets in different branches of the phylogenetic tree, and other target families. - significant activity in cells < 1 mM. - the co-crystal structure of the ligand and protein is solved to better than 2.8A resolution. - the chemical probe is widely available to the scientific community without restrictions on use.

Group Members

  • David Smil
  • Hong Wu
  • Hong Zeng
  • Elena Dobrovetsky
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

Accessing protein methyltransferase and demethylase enzymology using microfluidic capillary electrophoresis.
Wigle TJ, Provencher LM, Norris JL, Jin J, Brown PJ, Frye SV, Janzen WP
Chem. Biol.. 2010 17(7):695-704. doi: 10.1016/j.chembiol.2010.04.014
PMID: 20659682

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.. 2010 53(15):5844-57. doi: 10.1021/jm100478y
PMID: 20614940

2017

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

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

2016

Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8.
Judge RA, Zhu H, Upadhyay AK, Bodelle PM, Hutchins CW, Torrent M, Marin VL, Yu W, Vedadi M, Li F, Brown PJ, Pappano WN, Sun C, Petros AM
ACS Med Chem Lett. 08.12.2016 7(12):1102-1106. doi: 10.1021/acsmedchemlett.6b00303
PMID: 27994746

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

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

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

SET9-Mediated Regulation of TGF-β Signaling Links Protein Methylation to Pulmonary Fibrosis.
Elkouris M, Kontaki H, Stavropoulos A, Antonoglou A, Nikolaou KC, Samiotaki M, Szantai E, Saviolaki D, Brown PJ, Sideras P, Panayotou G, Talianidis I
Cell Rep. 08.06.2016 . doi: 10.1016/j.celrep.2016.05.051
PMID: 27292644

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

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

Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
Agarwal P, Alzrigat M, Párraga AA, Enroth S, Singh U, Ungerstedt J, Österborg A, Brown PJ, Ma A, Jin J, Nilsson K, Öberg F, Kalushkova A, Jernberg-Wiklund H
Oncotarget. 07.01.2016 . doi: 10.18632/oncotarget.6843
PMID: 26755663

2015

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

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

Open access chemical probes for epigenetic targets.
Brown PJ, Müller S
Future Med Chem. 23.09.2015 . doi: 10.4155/fmc.15.127
PMID: 26397018

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

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

Tankyrase 1 Inhibitors with Drug-like Properties Identified by Screening a DNA-Encoded Chemical Library.
Samain F, Ekblad T, Mikutis G, Zhong N, Zimmermann M, Nauer A, Bajic D, Decurtins W, Scheuermann J, Brown PJ, Hall J, Gräslund S, Schüler H, Neri D, Franzini RM
J. Med. Chem.. 10.06.2015 . doi: 10.1021/acs.jmedchem.5b00432
PMID: 26061013

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

Identification of Structure-Activity Relationships from Screening a Structurally Compact DNA-Encoded Chemical Library.
Franzini RM, Ekblad T, Zhong N, Wichert M, Decurtins W, Nauer A, Zimmermann M, Samain F, Scheuermann J, Brown PJ, Hall J, Gräslund S, Schüler H, Neri D
Angew. Chem. Int. Ed. Engl.. 03.02.2015 . doi: 10.1002/anie.201410736
PMID: 25650139

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

Structure-activity relationship studies of SETD8 inhibitors.
Ma A, Yu W, Xiong Y, Butler KV, Brown PJ, Jin J
Medchemcomm. 03.01.2015 5(12):1892-1898. doi: 10.1039/C4MD00317A
PMID: 25554733

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

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

A scintillation proximity assay for histone demethylases.
Yu W, Eram MS, Hajian T, Szykowska A, Burgess-Brown N, Vedadi M, Brown PJ
Anal. Biochem.. 08.07.2014 . doi: 10.1016/j.ab.2014.06.023
PMID: 25010373

Discovery and development of potent and selective inhibitors of histone methyltransferase g9a.
Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C, Vedadi M, Michaelides MR, Chiang GG, Pappano WN
ACS Med Chem Lett. 13.02.2014 5(2):205-9. doi: 10.1021/ml400496h
PMID: 24900801

Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a
Sweis RF, Pliushchev M, Brown PJ, Guo J, Li F, Maag D, Petros AM, Soni NB, Tse C, Vedadi M, Michaelides MR, Chiang GG, PappanoWN
ACS Med. Chem. Lett. 04.01.2014 . doi:
PMID:

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

Identification of Novel Functionally Selective Kappa Opioid Receptor Scaffolds.
White KL, Scopton AP, Rives ML, Bikbulatov RV, Polepally PR, Brown PJ, Kenakin T, Javitch JA, Zjawiony JK, Roth BL
Mol. Pharmacol.. 10.10.2013 . doi: 10.1124/mol.113.089649
PMID: 24113749

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

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

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

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

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

Sinefungin derivatives as inhibitors and structure probes of protein lysine methyltransferase SETD2.
Zheng W, Ibáñez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A, Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M
J. Am. Chem. Soc.. 31.10.2012 134(43):18004-14. doi: 10.1021/ja307060p
PMID: 23043551

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

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

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

2010

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

Accessing protein methyltransferase and demethylase enzymology using microfluidic capillary electrophoresis.
Wigle TJ, Provencher LM, Norris JL, Jin J, Brown PJ, Frye SV, Janzen WP
Chem. Biol.. 30.07.2010 17(7):695-704. doi: 10.1016/j.chembiol.2010.04.014
PMID: 20659682

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

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