Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound

被引：107

作者：

Mitchell, Lorna H. ^{[1
]}

Drew, Allison E. ^{[1
]}

Ribich, Scott A. ^{[1
]}

Rioux, Nathalie ^{[1
]}

Swinger, Kerren K. ^{[1
]}

Jacques, Suzanne L. ^{[1
]}

Lingaraj, Trupti ^{[1
]}

Boriack-Sjodin, P. Ann ^{[1
]}

Waters, Nigel J. ^{[1
]}

Wigle, Tim J. ^{[1
]}

Moradei, Oscar ^{[1
]}

Jin, Lei ^{[1
]}

Riera, Tom ^{[1
]}

Porter-Scott, Margaret ^{[1
]}

Moyer, Mikel P. ^{[1
]}

Smith, Jesse J. ^{[1
]}

Chesworth, Richard ^{[1
]}

Copeland, Robert A. ^{[1
]}

机构：

[1] Epizyme Inc, Cambridge, MA 02138 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2015年 / 6卷 / 06期

关键词：

PRMT6; protein methyltransferase; oncology; tool compound; GENE-EXPRESSION; METHYLATION; REGULATOR; H3K4;

D O I：

10.1021/acsmedchemlett.5b00071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.

引用

收藏

页码：655 / 659

页数：5

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