PF-06939999

PF-06939999 is an orally available small-molecule inhibitor of protein arginine N-methyltransferase 5 (PRMT5), a histone methyltransferase enzyme that catalyzes the formation of monomethylated and symmetrical dimethylated arginine residues on histones H2A, H3 and H4 as well as other protein substrates. PRMT5 is overexpressed in several cancers and contributes to tumor cell proliferation by modulating gene expression. By inhibiting PRMT5's methyltransferase activity, PF-06939999 decreases levels of these methylated arginine residues leading to altered gene expression that may increase antiproliferative genes and/or decrease pro-proliferative genes. This results in potential antiproliferative and antineoplastic effects against rapidly dividing cancer cells. The drug was developed by Pfizer primarily for treatment of advanced or metastatic solid tumors including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), bladder cancer among others. Clinical trials showed dose-dependent inhibition of PRMT5 activity with manageable toxicities such as anemia and thrombocytopenia; partial tumor responses were observed in some patients with NSCLC and HNSCC[1][2][3][5][6][7]. The development program was discontinued for NSCLC based on strategic portfolio decisions but clinical data support PRMT5 as a validated oncology target[4][7].

Other names

1,2-Cyclopentanediol, 3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diolPRMT5 Inhibitor PF-06939999PRMT-5 Inhibitor PF-06939999PRMT 5 Inhibitor PF-06939999