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Mitchell LH, Drew AE, Ribich SA, et al. Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound. ACS Med Chem Lett. 2015;6(6):655-9doi: 10.1021/acsmedchemlett.5b00071.
Mitchell, L. H., Drew, A. E., Ribich, S. A., Rioux, N., Swinger, K. K., Jacques, S. L., Lingaraj, T., Boriack-Sjodin, P. A., Waters, N. J., Wigle, T. J., Moradei, O., Jin, L., Riera, T., Porter-Scott, M., Moyer, M. P., Smith, J. J., Chesworth, R., & Copeland, R. A. (2015). Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound. ACS medicinal chemistry letters, 6(6), 655-9. https://doi.org/10.1021/acsmedchemlett.5b00071
Mitchell, Lorna H, et al. "Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound." ACS medicinal chemistry letters vol. 6,6 (2015): 655-9. doi: https://doi.org/10.1021/acsmedchemlett.5b00071
Mitchell LH, Drew AE, Ribich SA, Rioux N, Swinger KK, Jacques SL, Lingaraj T, Boriack-Sjodin PA, Waters NJ, Wigle TJ, Moradei O, Jin L, Riera T, Porter-Scott M, Moyer MP, Smith JJ, Chesworth R, Copeland RA. Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound. ACS Med Chem Lett. 2015 Apr 06;6(6):655-9. doi: 10.1021/acsmedchemlett.5b00071. eCollection 2015 Jun 11. PMID: 26101569; PMCID: PMC4468411.
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ACS Med Chem Lett. 2015 Apr 06;6(6):655-9. doi: 10.1021/acsmedchemlett.5b00071. eCollection 2015 Jun 11.

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

ACS medicinal chemistry letters

Lorna H Mitchell, Allison E Drew, Scott A Ribich, Nathalie Rioux, Kerren K Swinger, Suzanne L Jacques, Trupti Lingaraj, P Ann Boriack-Sjodin, Nigel J Waters, Tim J Wigle, Oscar Moradei, Lei Jin, Tom Riera, Margaret Porter-Scott, Mikel P Moyer, Jesse J Smith, Richard Chesworth, Robert A Copeland

Affiliations

  1. Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.

PMID: 26101569 PMCID: PMC4468411 DOI: 10.1021/acsmedchemlett.5b00071

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.

Keywords: PRMT6; oncology; protein methyltransferase; tool compound

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