A Potent, Selective and Cell-Active Allosteric Inhibitor of Protein Arginine Methyltransferase 3 (PRMT3)
Dr. H. Ümit Kaniskan, Dr. Magdalena M. Szewczyk, Dr. Zhengtian Yu, Dr. Mohammad S. Eram, Dr. Xiaobao Yang, Keith Schmidt, Dr. Xiao Luo, Miao Dai, Dr. Feng He, Irene Zang, Dr. Ying Lin, Dr. Steven Kennedy, Dr. Fengling Li, Elena Dobrovetsky, Aiping Dong, Dr. David Smil, Dr. Sun-Joon Min, Dr. Melissa Landon, Dr. Jennifer Lin-Jones, Dr. Xi-Ping Huang, Prof. Dr. Bryan L. Roth, Prof. Dr. Matthieu Schapira, Dr. Peter Atadja, Dr. Dalia Barsyte-Lovejoy, Prof. Dr. Cheryl H. Arrowsmith, Dr. Peter J. Brown, Dr. Kehao Zhao, Prof. Dr. Jian Jin and Prof. Dr. Masoud Vedadi
Article first published online: 27 FEB 2015 | DOI: 10.1002/anie.201412154
High selectivity: The first PRMT3 chemical probe, SGC707, was discovered by structure-based optimization. SGC707 is a potent PRMT3 inhibitor with outstanding selectivity. The mechanism of action studies and crystal structure of the PRMT3–SGC707 complex confirm the allosteric inhibition mode. SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies.