PRMT5 Inhibitor

PRMT5-IN-45 (compound 36) is a potent and selective PRMT5 inhibitor with an IC₅₀ of 3 nM. PRMT5-IN-45 potently reduces the level of symmetric dimethylarginines (sDMA) and inhibits the proliferation of MOLM-13 cell lines by inducing apoptosis and cell cycle arrest.

PRMT5-IN-43 (compound 4A) is a PRMT5 inhibitor. PRMT5-IN-43 can be used in cancer research.

PRMT5-MTA-IN-5 (Compound 7) is an orally active, irreversible PRMT5-MTA complex (PRMT5•MTA) inhibitor (IC₅₀=1.15 nM). PRMT5-MTA-IN-5 blocks arginine methylation and inhibits ribosomal RNA processing and cell cycle-related protein expression. PRMT5-MTA-IN-5 potently inhibits proliferation in MTAP-deficient tumor cells. PRMT5-MTA-IN-5 is promising for research of MTAP-deficient solid tumors, such as liver, breast, and pancreatic cancers.

PRMT5-IN-44 (compound 12) is a PRMT5 inhibitor. PRMT5-IN-44 can be used in cancer research.

PRMT5-IN-9 is a novel PRMT5 inhibitor for researching cancer, with an IC₅₀ of 0.01 μM.

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-23 (compound 50) is an inhibitor of protein arginine methyltransferase 5 (PRMT5) with anti-tumor activity. PRMT5 is a type of protein arginine methyltransferase, and is a new anti-tumor target related to epigenetic modification.

PRMT5-IN-49 (Compound 4b16) is an inhibitor of PRMT5.

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.

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

PRMT5-IN-36-d3 is the deuterated derivative of PRMT5-IN-36. PRMT5-IN-36-d3 (compound 4) is an orally active PRMT5 inhibitor for cancer research.

PRMT5-IN-53 is a gut-restricted and orally active PRMT5 inhibitor with pIC₅₀s of ≥ 9.7 against hPRMT5 and mPRMT5. PRMT5-IN-53 binds to the PRMT5:MEP50 complex with a K_D of 11.3 pM. PRMT5-IN-53 effectively inhibits PRMT5 locally in the intestines of mice, significantly reducing the number and area of polyps, while avoiding systemic hematological toxicity (such as anemia, neutropenia). PRMT5-IN-53 can be used for the study of colorectal cancer especially for familial adenomatous polyposis (FAP).

PRMT5-IN-58 is an MTA-cooperative PRMT5 inhibitor and PRMT5-MTA complex binder (IC₅₀ = 11.7 nM) that inhibits methyltransferase activity and SDMA (HY-101410) production by stabilizing the MTA-bound conformation, and induces apoptosis via sub-G1 phase accumulation, exhibiting selective antiproliferative activity against MTAP-deleted cancer cells over MTAP wild-type cells. PRMT5-IN-58 can be used for research on MTAP-deleted cancers.

TNG456 is an orally active, CNS-penetrant, selective, MTA-cooperative PRMT5 inhibitor. TNG456 drives dose-dependent antitumor activity in mouse xenograft models. TNG456 can be used for the research of MTAP-null solid tumors, including gliomas, and CNS metastases.

GSK3326595 succinate (EPZ015938 succinate) is a protein arginine methyltransferase 5 (PRMT5) inhibitor. GSK3326595 succinate decreases SARS-CoV-2 infection, inhibits cancer cell proliferation and induces pro-inflammatory macrophage polarization and increases hepatic triglyceride levels without affecting atherosclerosis. GSK3326595 succinate can be used for research of relapsed/refractory mantle cell lymphoma.