prmt5 in 11

PRMT5-IN-11 demonstrates potent structure-dependent inhibition against the protein methyltransferase PRMT5:MEP50 complex at submicromolar concentrations.

MRTX9768 hydrochloride is a potent, orally active PRMT5 inhibitor. MRTX9768 hydrochloride is a synthetic lethal-based inhibitor binding the PRMT5-MTA complex[1]. MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC50 3 nM; prolif. IC50 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC50 544 nM; prolif. IC50 861 nM)[1].MRTX9768 selectively targets MTAP CDKN2A-deleted tumors[2][1]. In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow[1]. [1]. Christopher R. Smith, et al. Abstract LB003: Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP CDKN2A-deleted tumors. AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA.[2]. Yingqing Chen, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother. 2021 Oct 4;144:112252.

PRMT5-IN-1 is a covalent inhibitor of protein arginine methyltransferase 5 (PRMT5)(IC50 of 11 nM for PRMT5 MEP50).

PRMT5 IN-1 hydrochloride (compound 9) is a hemiacetalamine and a potent inhibitor of selective protein arginine methyltransferase 5 (PRMT5), exhibiting an inhibitory effect on PRMT5 MEP50 with an IC50 of 11 nM. Under physiological conditions, it can be converted to an aldehyde and reacts with C449 to form a covalent adduct.