PF-06939999 (PF06939999) is a potent, selective, S-adenosylmethionine (SAM) competitive PRMT5 inhibitor with SPR Kd of 5.8 pM.
PF-06939999 displays at least one million-fold selective for PRMT5 over a panel of protein methyltransferases and 20 diverse protein kinases.
PF-06939999 demonstrates dose-dependent reduction of symmetric dimethyl arginine (SDMA) and an antiproliferative response in A2780 cells (IC50=3.3 nM).
PF-06939999 showed dose-dependent loss of SDMA on several proteins, with a cellular IC50 1.1 nM in A427 cells.
PF-06939999 demonstrates tumor growth inhibition in splicing mutant NSCLC (oral 3, 10, and 30 mg/kg).
