prmt5-in-1

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.

PRMT5/EGFR-IN-1 (Compound 10p) is an orally active dual inhibitor targeting PRMT5 and EGFR, with IC50 values of 15.47 μM and 19.31 μM, respectively. It demonstrates antiproliferative activity against the A549, MCF7, HeLa, and MDA-MB-231 cell lines. This compound also exhibits favorable pharmacokinetic (PK) and pharmacodynamic (PD) properties in vivo and significantly inhibits the growth of MCF7 orthotopic xenograft tumors.

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-IN-19 (Compound 41) is a potent, orally active PRMT5 inhibitor, exhibiting selectivity towards the SAM-binding pocket of PRMT5 with IC50 values of 23.9 nM (radioactive biochemical assay) and 47 nM (AlphaLISA assay). It effectively blocks methyltransferase activity and demonstrates high specificity against other PRMTs and PKMTs, exerting anti-proliferative effects through apoptosis induction and holding potential in cancer-related research [1].

PRMT5-IN-14 is a PRMT5 inhibitor used to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

PRMT5-IN-13 is a selective inhibitor of protein arginine methyltransferase 5 (PRMT5).

PRMT5-IN-15, a PRMT5 inhibitor, has an IC50 value of 0.84 nM.

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

PRMT5-IN-12 demonstrates significant inhibitory activity on PRMT5.

PRMT5-IN-10 exhibits promising structure-dependent inhibitory effect on the protein methyltransferase PRMT5:MEP50 complex.

PRMT5-IN-17 (Compound 6) is a PRMT5 inhibitor with antitumor activity; PRMT5, a protein arginine methyltransferase, is a novel anticancer target linked to epigenetic modifications.

PRMT5-IN-16 (Compound 20) is a PRMT5 inhibitor with antitumor effects, targeting the protein arginine methyltransferase PRMT5, which is a novel anti-tumor target associated with epigenetic modifications.

PRMT5-IN-18 (Compound 002) is a potent inhibitor of PRMT5, useful in studying PRMT5-mediated diseases such as tumors.

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

PRMT5ligand 1 is a ligand of PRMT5, used as a target protein ligand in the synthesis of the PROTAC degrader MS4322.

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-4 (compound AAA-1) is a PRMT5 inhibitor. This chemical compound specifically impedes the activity of PRMT5, an enzyme involved in the methylation of arginine residues on target proteins, which plays a critical role in various cellular processes.

PRMT5-IN-21 (compound 1) is a potent inhibitor of the cyclonucleoside enzyme PRMT5.

PRMT5-IN-22 (compound 53), an inhibitor of protein arginine methyltransferase 5 (PRMT5), exhibits anti-tumor activity. As a protein arginine methyltransferase, PRMT5 represents a novel anti-tumor target associated with epigenetic modification [1].

PRMT5-IN-23 (compound 50), an inhibitor of protein arginine methyltransferase 5 (PRMT5), exhibits anti-tumor activity. As a novel anti-tumor target associated with epigenetic modification, PRMT5 belongs to the protein arginine methyltransferase family [1].

PRMT5-IN-25 (compound 503) is a potent PRMT5 inhibitor with an inhibition constant (K i) of 0.06 nM and demonstrated antiproliferative properties [1].

PRMT5-IN-29 is a potent, orally active inhibitor of PRMT5, exhibiting an IC50 value of 1.5 μM, showing promise for use in advanced cancer research [1].

PRMT5-IN-28 (compound 36) serves as an inhibitor of the protein arginine methyltransferase 5 (PRMT5) enzyme, which is involved in gene transcription, mRNA splicing, DNA repair, protein localization, cell fate determination, and signal transduction. Dysregulated PRMT5 activity contributes to oncogenesis by promoting cancer cell proliferation, apoptosis resistance, invasion, metastasis, and impacting immune evasion [1].