PRMT5 Inhibitor

DW14800 is a protein arginine methyltransferase 5 (PRMT5) inhibitor, with an IC₅₀ of 17 nM. DW14800 reduces H4R3me2s levels and enhances the transcription of HNF4α, but does not alter PRMT5 expression. Anti-cancer activity.

PRMT5 IN-1 hydrochloride (compound 9), a hemiaminal, is a potent, selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC₅₀ of 11 nM for PRMT5/MEP50. PRMT5 IN-1 hydrochloride can be converted to aldehydes and react with C449 to form covalent adducts under physiological conditions.

PRMT5-IN-20 (P31 Claim 1) is a selective inhibitor of protein arginine methyltransferase 5 (PRMT5), and it can be used in cancer research.

WX2-43 is a PRMT5-KLF4 inhibitor (K_d of 11.0 nM). WX2-43 binds to the region between amino acids L400-M500 on PRMT5. WX2-43 efficiently intercepts the interaction between KLF4 and PRMT5, and blocks KLF4 methylation. WX2-43 decreases p21 levels and increases Bax levels. WX2-43 suppresses triple negative breast tumor progression. WX2-43 can be used in the research of triple-negative breast cancer and colorectal cancer.

PRMT5 IN-1, a hemiaminal, is a potent, selective protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC₅₀ of 11 nM for PRMT5/MEP50. PRMT5 IN-1 can be converted to aldehydes and react with C449 to form covalent adducts under physiological conditions.

MRTX9768 hydrochloride is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor.

PRMT5-IN-4 is a PRMT5 inhibitor. PRMT5-IN-4 is applicable for cancer research.

PRT543 is an orally active selective PRMT5 inhibitor. PRT543 reduces intracellular symmetric dimethylarginine (sDMA) levels, downregulates the expression of genes related to DNA damage repair and DNA replication pathways, and induces abnormal alternative splicing. PRT543 inhibits the MYB, NOTCH1 and PI3K/AKT signaling pathways, promotes nuclear translocation of FOXO1, upregulates the pro-apoptotic protein BAX, and enhances cellular sensitivity to BCL-2 inhibition. PRT543 disrupts the normal RNA splicing process and exerts a synthetic lethal effect on myeloid tumor cells carrying splicing factor mutations. PRT543 can be used in research related to various cancers including breast cancer, ovarian cancer and acute myeloid leukemia.

PRMT5-MTA-IN-1 (Compound A9a) is an inhibitor for protein arginine methyltransferase PRMT5-MTA. PRMT5-MTA-IN-1 inhibits the proliferation of colorectal cancer cell HCT116 wildtype and MTAP del mutant, with an IC₅₀ of 16 nM and 2.47 μM. PRMT5-MTA-IN-1 exhibits good liver microsomal stability and film permeability. PRMT5-MTA-IN-1 exhibits good pharmacokinetic characteristics in CD-1 mice.

PRMT5-IN-39-d3 is the deuterated form of PRMT5-IN-39. PRMT5-IN-39-d3 is an orally active PRMT5 inhibitor and can be used for study of cancer.

PRMT5-IN-57 is an orally active andselective MTA-cooperative PRMT5 inhibitor, with an IC₅₀ of 8.39 nM against PRMT5/MTA complex. PRMT5-IN-57 exhibits potent and selective antiproliferative activity against MTAP-null cancer cells. PRMT5-IN-57 demonstrates significant in vivo antitumor efficacy in an HCT116 MTAP-/- CDX model. PRMT5-IN-57 can be used for the research of MTAP-deleted cancers.

PARP1/PRMT5-IN-1 is an inhibitor of PARP1 and PRMT5, with an IC₅₀ of 0.60 nM against PARP1 and an IC₅₀ of 4.67 nM against PRMT5. PARP1/PRMT5-IN-1 downregulates the homologous recombination (HR)-associated factors BRCA1, BRCA2, and RAD51, thereby suppressing homologous recombination function. PARP1/PRMT5-IN-1 induces the accumulation of DNA double-strand breaks. PARP1/PRMT5-IN-1 triggers apoptosis. PARP1/PRMT5-IN-1 is applicable for breast cancer research.

PRMT5-IN-28 (compound 36) is an inhibitor of protein arginine methyltransferase 5 (PRMT5) enzyme. Protein arginine methylation is a common post-translational modification involved in gene transcription, mRNA splicing, DNA repair, protein cellular localization, cell fate determination and signal transduction, etc. Abnormal PRMT5 can promote cancer cell proliferation, resist apoptosis, enhance invasion and metastasis, and affect immune escape.

PRMT5-IN-52 (Compound 17) is a non-nucleoside Protein Arginine Methyltransferase 5 (PRMT5) inhibitor with inhibitory rates of 20.2% at 10 μM. PRMT5-IN-52 has potent antitumor activity, promising for research of cancers, including lung, prostate cancer, and colorectal carcinoma.

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

PRMT5-IN-47 (compound 20) is a potent, selectively and orally active, MTA cooperative PRMT5 inhibitor with an IC₅₀ value of 15 nM. PRMT5-IN-47 shows antiproliferative activity. PRMT5-IN-47 shows anticancer activity.

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.

PRMT5-MTA-IN-4 (Compound 30) is a potent irreversible protein arginine methyltransferase 5 (PRMT5) inhibitor (IC₅₀=8 nM). PRMT5-MTA-IN-4 blocks arginine methylation, inhibiting ribosomal RNA processing and cell cycle-related protein expression. PRMT5-MTA-IN-4 exhibits antiproliferative activity in multiple tumor cell lines (e.g., IC₅₀=0.3 μM in DLD-1 cells). PRMT5-MTA-IN-4 is promising for research of hematological malignancies, such as acute myeloid leukemia, diffuse large B-cell lymphoma.

PRMT5-IN-54 (example 92a) is a protein arginine methyltransferase 5 (PRMT5) inhibitor. PRMT5-IN-54 can be used for the study of autoimmune diseases.

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.