prmt5-mta

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

PRMT5-MTA-IN-3 (Compound P2A) is an orally active and selective inhibitor of protein arginine methyltransferase 5 (PRMT5). It inhibits the proliferation of MTAP-deficient colorectal cancer HCT-116 cell line with an IC50 value of 5 nM. PRMT5-MTA-IN-3 holds potential for research in cancers, particularly in MTAP-deficient tumors such as colorectal cancer, non-small cell lung cancer, and pancreatic cancer.

PRMT5-MTA-IN-1 (Compound A9a) is an inhibitor of the protein arginine methyltransferase PRMT5-MTA. It suppresses the proliferation of colorectal cancer cells HCT116, both wild-type and MTAP del mutants, with IC50 values of 16 nM and 2.47 μM, respectively. Additionally, PRMT5-MTA-IN-1 demonstrates favorable hepatic microsomal stability, membrane permeability, and pharmacokinetic properties in CD-1 mice.

PRMT5-MTA-IN-4 (Compound 30) is a potent irreversible inhibitor of protein arginine methyltransferase 5 (PRMT5) with an IC50 of 8 nM. It obstructs arginine methylation, hinders ribosomal RNA processing, and suppresses cell cycle-related protein expression. This compound shows antiproliferative activity in various tumor cell lines, exemplified by an IC50 of 0.3 μM in DLD-1 cells. PRMT5-MTA-IN-4 holds potential for research into hematological malignancies such as acute myeloid leukemia and diffuse large B-cell lymphoma.

PRMT5-MTA-IN-5 (Compound 7) is an orally active, irreversible inhibitor of the PRMT5-MTA complex (PRMT5•MTA) with an IC50 value of 1.15 nM. It effectively blocks arginine methylation, impedes the processing of ribosomal RNA, and suppresses the expression of proteins related to the cell cycle. PRMT5-MTA-IN-5 significantly inhibits the proliferation of tumor cells lacking MTAP and shows potential for research into MTAP-deficient solid tumors, such as liver, breast, and pancreatic cancers.

PRMT5-MTA-IN-6 (Compound 31) is a selective inhibitor of PRMT5 in conjunction with MTA, exhibiting potent inhibitory activity against PRMT5・MTA with an IC50 of 6.6 nM. It selectively inhibits the growth of MTAP-deficient HCT-116 cells with an IC50 of 319 nM and is useful for studying MTAP-deficient tumors.

MRTX-9768 is a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors.

MRTX-1719 is a potent and selective inhibitor of the PRMT5/MTA complex with an IC50 value of <10 nM against PRMT5/MTAMTAPDELSDMA cell lines.

PRMT5-IN-47 (compound 20) is a potent, selective, and orally active MTA co-operative PRMT5 inhibitor, with an IC50 value of 15 nM. It exhibits antiproliferative and anticancer activity.

PRMT5-IN-34 (Compound C) is an inhibitor of MTA-cooperative protein arginine methyltransferase 5 (PRMT5/MAT).

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.

TNG-462 is a potent and selective PRMT5 inhibitor with antitumor activity and oral activity, primarily for the treatment of methylthioadenosine phosphorylase (MTAP)-deficient and/or methylthioadenosine (MTA)-accumulating cancers (e.g., non-small-cell lung cancer, pancreatic cancer, bladder cancer, and hematologic malignancies).

AMG-193 is an inhibitor of the MTA-PRMT5 complex and is used in the study of cancer, respiratory diseases and digestive disorders.

AZ-PRMT5i-1 (Compound 28) is an effective, orally-active MTAP-selective PRMT5 inhibitor. It exhibits synergistic properties with MTA and demonstrates anti-tumor activity both in vivo and in vitro, making it suitable for research in cancers lacking MTAP.