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

ABSTRACT: 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.

SUBMITTER: Mitchell LH

PROVIDER: S-EPMC4468411 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Mitchell Lorna H LH Drew Allison E AE Ribich Scott A SA Rioux Nathalie N Swinger Kerren K KK Jacques Suzanne L SL Lingaraj Trupti T Boriack-Sjodin P Ann PA Waters Nigel J NJ Wigle Tim J TJ Moradei Oscar O Jin Lei L Riera Tom T Porter-Scott Margaret M Moyer Mikel P MP Smith Jesse J JJ Chesworth Richard R Copeland Robert A RA

ACS medicinal chemistry letters 20150406 6

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 sho ...[more]

PMID: 26101569

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