prmt5 in 2

PRMT5-IN-2 is an inhibitor of protein arginine methyltransferase 5.

PRMT5-MTA-IN-2 (compound 1) is a synergistic inhibitor of PRMT5 with an IC50 of less than 1.5 nM.

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-31 (Compound 3m), a selective PRMT5 inhibitor (IC50: 0.31 μM), increases hnRNP E1 protein levels by occupying the substrate site of PRMT5 and establishing key interactions with amino acid residues. It exhibits antiproliferative properties against A549 cells through induction of apoptosis and inhibition of cell migration, while demonstrating high metabolic stability in human liver microsomes (T1 2: 132.4 min) [1].

Antiproliferative Agent-25 (Compound 3s4) is a selective PRMT5 inhibitor displaying an IC50 of 0.11 μM. It elevates hnRNP E1 protein levels and forms hydrogen bond interactions with SAM and the E444 residue of PRMT5. This compound exhibits antiproliferative effects in A549 cells by inducing apoptosis and inhibiting migration, albeit it presents high clearance rates, with half-lives of 21.8 minutes in human liver microsomes and 4.7 minutes in rat liver microsomes [1].