TP-064, a potent and selective small molecule inhibitor of PRMT4 for multiple myeloma.

ABSTRACT: Protein arginine methyltransferase (PRMT) 4 (also known as coactivator-associated arginine methyltransferase 1; CARM1) is involved in a variety of biological processes and is considered as a candidate oncogene owing to its overexpression in several types of cancer. Selective PRMT4 inhibitors are useful tools for clarifying the molecular events regulated by PRMT4 and for validating PRMT4 as a therapeutic target. Here, we report the discovery of TP-064, a potent, selective, and cell-active chemical probe of human PRMT4 and its co-crystal structure with PRMT4. TP-064 inhibited the methyltransferase activity of PRMT4 with high potency (half-maximal inhibitory concentration, IC₅₀ < 10 nM) and selectivity over other PRMT family proteins, and reduced arginine dimethylation of the PRMT4

SUBMITTER: Nakayama K 

PROVIDER: S-EPMC5915086 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature