mtap

AGI-24512 is a potent inhibitor of methionine adenylyltransferase 2α (MAT2A) (IC50: 8 nM).AGI-24512 shows antiproliferative activity in MTAP-deficient cancer cells.AGI-24512 inhibits MAT2A, which causes DNA damage in MTAP, and is often used in conjunction with anticancer compounds in cancer research.

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

MT-DADMe-ImmA (MTDIA) is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP, Ki: 90 pM).

4-Methyl-2-oxopentanoic acid is an abnormal metabolite, a neurotoxin and a metabolic toxin.

DMTAP, a cationic lipid, facilitates the delivery of DNA, RNAi, and drugs [1] [2] [3].

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.

AGI-25696 is an inhibitor of methionine adenosyltransferase 2A (MATA2). AGI-25696 blocks the growth of MTAP-deleted tumors in vivo and can be used for studies about the treatment of cancer.

L-Alanosine, an antibiotic isolated from the fermentation product of Streptomyces alanosinicus, inhibits tumor cell proliferation by blocking the adenylosuccinate synthetic pathway through the inhibition of adenylosuccinate synthetase and Methylthioadenosine phosphorylase.

MAT2A-IN-16 is a MAT2A inhibitor that effectively suppresses the proliferation of MTAP-/-HCT-116 cells, with an IC50 value of 20 nM.

MAT2A-IN-21 (compound 28) is a potent inhibitor of methionine adenosyltransferase 2A (MAT2A), with an IC50 of 49 nM. It selectively inhibits cancer cells with MTAP deficiency.

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.

MAT2A-IN-24 (Compound 9) is an inhibitor of methionine adenosyltransferase 2a (MAT2a), with an IC50 value of 20 nM for MAT2a inhibition and an antiproliferative IC50 value of 10 nM for HAP1MTAP–/– cells. MAT2A-IN-24 is applicable in the research of tumor diseases associated with MTAP deficiency.

m-APTA (5'-S-(3-aminophenyl)-5'-thioadenosine) is a selective chemoprotective agent targeting methylthioadenosine phosphorylase (MTAP). It can be converted into adenine, which is a crucial step in shielding normal cells from the toxicity of nucleobase analogs (NBA). m-APTA holds potential for research in MTAP-deficient cancers.

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-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.

ZS34 is a potent, orally active, and selective inhibitor of MAT2A, with an IC50 value of 13.7 nM, and it exhibits minimal inhibition of hERG and UGT1A1. By inhibiting SAM synthesis, reducing SDMA levels, and inducing DNA damage, ZS34 selectively inhibits the growth of methylthioadenosine phosphorylase (MTAP)-deficient cancer cells. It demonstrates antitumor activity in HCT116 MTAP-/- xenograft mouse models and is suitable for research on MTAP-deficient cancers.

PRMT5-MTA-IN-7 (Compound 14) is a selective inhibitor of PRMT5-MTA. It exhibits KD values of 236 nM for PRMT5-MTA and 2.84 μM for PRMT5-SAM, with IC50 values of 4.08 μM and 13.6 μM, respectively. PRMT5-MTA-IN-7 selectively inhibits the proliferation of MTAP-deficient cancer cells and is applicable in colon cancer research.

ERG-IN-4 (Compound 12) is an orally active, selective ERG inhibitor with an IC50 value of 5.2 μM for hERG. It activates PXR and exhibits anticancer properties against non-small cell lung cancer lacking MTAP.

PRMT5-MTA-IN-8 is an orally active inhibitor of the PRMT5-MTA complex with an IC50 of 4.4 nM. It effectively inhibits the production of symmetric dimethylarginine (SDMA) within cells and suppresses the proliferation of MTAP-deficient cells. In a mouse model of triple-negative breast cancer, PRMT5-MTA-IN-8 demonstrates antitumor efficacy by inhibiting PRMT5, reducing SDMA levels, and inducing tumor cell apoptosis (Apoptosis). This compound is applicable for research in cancers such as triple-negative breast cancer.

Erythrofuranosyladenine(9-beta-D-Erythrofuranosyladenine, ETA) is a nontoxic MTAP substrate. Erythrofuranosyladenine is an effective salvage agent for methylthioadenosine phosphorylase–selective therapy of T-cell acute lymphoblastic leukemia with L-alanos

MTDIA (MT-DADMe-ImmA and methylthio-DADMe-Immucillin A) is an MTAP inhibitor.

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.

MAT2A-IN-5, a potent inhibitor of MAT2A, effectively targets the abnormally elevated expression of MAT2A found in various tumor types such as gastric, colon, liver, and pancreatic cancers. By reducing the proliferative activity of MTAP-deficient cancer cells, MAT2A-IN-5 exhibits potential in cancer research applications [1].