PRMT1 Inhibitor

MS023, a chemical probe, is a potent, selective, and cell-active inhibitor of human type I protein arginine methyltransferases (PRMTs) inhibitor, with IC₅₀s of 30, 119, 83, 4 and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively.

GSK3368715 dihydrochloride (EPZ019997 dihydrochloride) is an orally active, reversible, and S-adenosyl-L-methionine (SAM) uncompetitive type I protein arginine methyltransferases (PRMTs) inhibitor (IC₅₀=3.1 nM (PRMT1), 48 nM (PRMT3), 1148 nM (PRMT4), 5.7 nM (PRMT6), 1.7 nM (PRMT8)). GSK3368715 dihydrochloride (EPZ019997 dihydrochloride) produces a shift in arginine methylation states, alters exon usage, and has strong anti-cancer activity.

AMI-1 is a potent, cell-permeable and reversible inhibitor of protein arginine N-methyltransferases (PRMTs), with IC₅₀s of 8.8 μM and 3.0 μM for human PRMT1 and yeast-Hmt1p, respectively. AMI-1 exerts PRMTs inhibitory effects by blocking peptide-substrate binding.

TC-E 5003 is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC₅₀ of 1.5 µM against hPRMT1. TC-E 5003 modulates the lipopolysaccharide (LPS) (HY-D1056)-induced AP-1 and NF-κB signaling pathways with anti-inflammatory properties. TC-E 5003 also upregulates the expression of Ucp1 and Fgf21, activates protein kinase A signaling and lipolysis in primary subcutaneous adipocytes from both mouse and humans. TC-E 5003 is promising for research of obesity and associated metabolic disorders, oxidative stress, inflammation and cancers.

GSK3368715 (EPZ019997) is an orally active, reversible, and S-adenosyl-L-methionine (SAM) uncompetitive type I protein arginine methyltransferases (PRMTs) inhibitor (IC₅₀=3.1 nM (PRMT1), 48 nM (PRMT3), 1148 nM (PRMT4), 5.7 nM (PRMT6), 1.7 nM (PRMT8)). GSK3368715 (EPZ019997) produces a shift in arginine methylation states, alters exon usage, and has strong anti-cancer activity.

SKLB06489 is a selective and orally active inhibitor of type I PRMT enzymes, with IC₅₀ values of 64.55 nM (PRMT1), 4.21 nM (PRMT6), and 51.27 nM (PRMT8). SKLB06489 inhibits cell proliferation, colony formation, DNA replication, and DNA damage repair in cancer cells. SKLB06489 induces G0/G1-phase cell cycle arrest and apoptosis in cancer cells. SKLB06489 enhances intracellular cholesterol efflux via ABCA1 and ABCG1 upregulation, disrupts cholesterol metabolic homeostasis, and suppresses tumor growth in subcutaneous xenograft models. SKLB06489 can be used for the research of triple-negative breast cancer (TNBC).

MS3-123 is an orally active PRMT1 inhibitor (IC₅₀ = 11.4 nM) that selectively targets the unique Cys119 residue within the SAM-binding pocket. MS3-123 covalently binds to PRMT1 through a time-dependent irreversible mechanism and exhibits high selectivity over other PRMT family members and other methyltransferases. MS3-123 inhibits breast cancer cell proliferation, migration and invasion, and induces cell cycle arrest and apoptosis. MS3-123 is useful for breast cancer research.

Furamidine dihydrochloride (DB75 dihydrochloride) is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC₅₀ of 9.4 μM. Furamidine dihydrochloride is selective for PRMT1 over PRMT5, PRMT6, and PRMT4 (CARM1) (IC₅₀s of 166 µM, 283 µM, and >400 µM, respectively). Furamidine dihydrochloride is a potent, reversible and competitive tyrosyl-DNA phosphodiesterase 1 (TDP-1) inhibitor. Inhibition of TDP-1 by Furamidine dihydrochloride is effective both with single- and double-stranded DNA substrates but is slightly stronger with the duplex DNA. Furamidine dihydrochloride is also an antiparasite agent.

MS023 dihydrochloride is a potent, selective, and cell-active inhibitor of human type I protein arginine methyltransferases (PRMTs) inhibitor, with IC₅₀s of 30, 119, 83, 4 and 5 nM for PRMT1, PRMT3, PRMT4, PRMT6, and PRMT8, respectively.

DCLX069 is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC₅₀ value of 17.9 µM. DCLX069 shows less active against PRMT4 and PRMT6. DCLX069 has anticancer effects.

C-7280948 is a selective and potent protein methyltransferase1 (PRMT1) inhibitor with an IC₅₀ value of 12.75 μM.

AMI-408 is a PRMT1 inhibitor. AMI-408 can reduce H4R3me2as level in MLL-GAS7 leukemia cells.

GSK3368715 trihydrochloride (EPZ019997) is an orally active, reversible, and S-adenosyl-L-methionine (SAM) uncompetitive type I protein arginine methyltransferases (PRMTs) inhibitor (IC₅₀=3.1 nM (PRMT1), 48 nM (PRMT3), 1148 nM (PRMT4), 5.7 nM (PRMT6), 1.7 nM (PRMT8)). GSK3368715 trihydrochloride (EPZ019997) produces a shift in arginine methylation states, alters exon usage, and has strong anti-cancer activity.

PRMT4-IN-1 is a selective inhibitor of PRMT4 (IC₅₀=3.2 nM). PRMT4-IN-1 inhibits MCF7 relative viability.

PRMT5-IN-19 (Compound 41) is an selective orally active non-nucleoside PRMT5 inhibitor with IC₅₀ values of 23.9 nM (radioactive biochemical assay) and 47 nM (AlphaLISA assay). PRMT5-IN-19 can occupy the SAM-binding pocket in PRMT5 and block methyltransferase activity, which displays good selectivity over other PRMTs and PKMTs. PRMT5-IN-19 inhibits cell proliferation by inducing cell apoptosis, and can be used for cancer-related research.

PRMT1-IN-3 is a potent protein arginine methyltransferase 1 (PRMT1) inhibitor with an IC₅₀ of 4.11 μM. PRMT1-IN-3 inhibits PRMT6 and PRMT8 with IC₅₀s of 23.3 and 30.1 μM. PRMT1-IN-3 suppresses asymmetric dimethylarginine (ADMA) levels and histone H4R3me2a modification in triple-negative breast cancer (TNBC) cells. PRMT1-IN-3 induces cell cycle arrest, apoptosis, and inhibits migration and colony formation in MDA-MB-231 cells. PRMT1-IN-3 acts as chemotherapeutic sensitizers for Paclitaxel (HY-B0015). PRMT1-IN-3 can be used for the study of TNBC.

CARM1-IN-4 (compound 11f) is a potent CARM1 inhibitor with IC₅₀s of 9 nM and 56 nM for CARM1 and PRMT1, respectively. CARM1-IN-4 displays significant anti-proliferative effects on colorectal cancer cell lines. CARM1-IN-4 effectively inhibits the methyltransferase activity of CARM1 and prevents methylation of downstream proteins. CARM1-IN-4 induces apoptosis and shows antitumor activity.

PRMT5-IN-33 (compound A8) is a selective, SAM-competitve PRMT5 inhibitors with IC₅₀ of 10.9 nM. PRMT5-IN-33 induces apoptosis and inhibits proliferation of cells Z-138 and MOLM-13. PRMT5-IN-33 exhibits an antitumor activity.

4-Amino-N-(2-phenylethyl) benzamide is an inhibitor of human protein arginine methyltransferase 1 (hPRMT1) with an IC₅₀ of 49.7 μM. 4-Amino-N-(2-phenylethyl) benzamide can be used in epigenetics-related research as well as prostate cancer-related research.