4Y2H

Crystal structure of human protein arginine methyltransferase PRMT6 bound to SAH and an aryl pyrazole inhibitor

Summary for 4Y2H

• Entry DOI: 10.2210/pdb4y2h/pdb
• Related: 4Y30
• Descriptor: Protein arginine N-methyltransferase 6, S-ADENOSYL-L-HOMOCYSTEINE, N-{[5-(4-fluorophenyl)-1H-pyrazol-4-yl]methyl}-N-methylethane-1,2-diamine, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q96LA8
• Total number of polymer chains: 2
• Total formula weight: 80607.50

Authors

Swinger, K.K.,Boriack-Sjodin, P.A. (deposition date: 2015-02-09, release date: 2015-04-22, Last modification date: 2024-02-28)

Primary citation

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.
Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound.
Acs Med.Chem.Lett., 6:655-659, 2015

PubMed 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.

PubMed: 26101569
DOI: 10.1021/acsmedchemlett.5b00071

Experimental method

X-RAY DIFFRACTION (2.37 Å)