Histone Methyltransferase Inhibitor

AMG 193 is an orally active MTA-cooperative PRMT5 inhibitor with antitumor activity. AMG 193, when complexed with MTA, preferentially inhibits the growth of MTAP-deficient tumor cells by inhibiting PRMT5 (IC₅₀=0.107 μM), thereby protecting normal cells with wild-type MTAP.

Chaetocin is a specific inhibitor of the histone methyltransferase (HMT) SU(VAR)3-9 with an IC₅₀ of 0.6 μM for SU(VAR)3-9. It also inhibits thioredoxin reductase (TrxR) with an IC₅₀ of 4 μM.

EED226 is a polycomb repressive complex 2 (PRC2) inhibitor, which binds to the K27me3-pocket on embryonic ectoderm development (EED) and shows strong antitumor activity in xenograft mice model. EED226 is a potent, selective, and orally bioavailable EED inhibitor. EED226 inhibits PRC2 with an IC₅₀ of 23.4 nM when the H3K27me0 peptide is used as a substrate in the in vitro enzymatic assays.

Sinefungin is a potent inhibitor of virion mRNA(guanine-7-)-methyltransferase, mRNA(nucleoside-2'-)-methyltransferase, and viral multiplication. Sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4 methylation.

TNG-462 is an orally active and selective PRMT5 inhibitor with anti-tumor activity against methylthioadenosine phosphorylase (MTAP) deficiency and/or methylthioadenosine (MTA) accumulation cancers.

Gintemetostat (KTX-1001) is an orally active, highly specific NSD2/MMSET histone methyltransferase inhibitor with human NSD2 IC₅₀ values ranging 0.460-2.17 nM and NSD2 SET domain IC₅₀ of 2.32 nM and K_d values ranging 6.3-70.4 nM.Gintemetostat reduces H₃K₃₆me₂ levels, impairs multiple myeloma cell adhesion and colony formation, enhances cytotoxicity, boosts T-cell activation, and sensitizes resistant multiple myeloma cells to other agents.Gintemetostat can be used for the research of multiple myeloma and relapsed and refractory multiple myeloma.

F5446 (Compound 1) is a selective small molecule inhibitor of SUV39H1 methyltransferase. F5446 decreases H3K9me3 deposition at the FAS promoter, increases Fas expression and increases colorectal carcinoma cell sensitivity to FasL-induced apoptosis in vitro. F5446 suppresses human colon tumor xenograft growth in vivo.

A-196 is a potent and selective inhibitor of SUV420H1 and SUV420H2 with IC₅₀ values of 25 nM and 144 nM, respectively. A-196 inhibits SUV4-20 biochemically in a substrate-competitive manner. A-196 represents a first-in-class chemical probe of SUV4-20 to investigate the role of histone methyltransferases in genomic integrity.

EZM 2302 is a potent and orally active CARM1 inhibitor with an IC₅₀ value of 6 nM. EZM 2302 shows antiproliferative activity and anti-tumor activity. EZM 2302 inhibits PABP1 and SMB expression.

Rinzimetostat (ORIC-944) is a selective, orally active, allosteric inhibitor targeting the EED subunit of polycomb repressive complex 2 (PRC2). Rinzimetostat is synergistic with androgen receptor pathway inhibitors (ARPIs) for the study of metastatic prostate cancer.

Bleximenib (JNJ-75276617) is an orally active and selective menin-KMT2A inhibitor, with IC₅₀ values of 0.1 nM, 0.045 nM, and ≤0.066 nM for humans, mice, and dogs, respectively. Bleximenib can inhibit the proliferation and induce apoptosis and differentiation of tumor cells. Bleximenib can be used in the research of tumors such as leukemia.

MAK683 is an embryonic ectoderm development (EED) inhibitor extracted from patent US20160176882 A1, compound example 2. MAK683 exhibits IC₅₀s of 59, 89, 26 nM in EED Alphascreen binding, LC-MS and ELISA assay.

MT-DADMe-ImmA is an inhibitor of human 5'-methylthioadenosine phosphorylase (MTAP) with a K_i of 90 pM.

OTS186935 is a potent protein methyltransferase SUV39H2 inhibitor with an IC₅₀ of 6.49 nM. OTS186935 shows significant inhibition of tumor growth in mouse xenograft models without any detectable toxicity. OTS193320 regulates the production of γ-H2AX in cancer cells.

Bleximenib (JNJ-75276617) oxalate is an orally active and selective menin-KMT2A inhibitor, with IC₅₀ values of 0.1 nM, 0.045 nM, and ≤0.066 nM for humans, mice, and dogs, respectively. Bleximenib oxalate can inhibit the proliferation and induce apoptosis and differentiation of tumor cells. Bleximenib oxalate can be used in the research of tumors such as leukemia.

Pociredir (FTX-6058) is a potent and orally active inhibitor of Embryonic Ectoderm Development (EED). Pociredir can induce HbF protein expression in cell and murine models. Pociredir can be used for the research of select hemoglobinopathies, including sickle cell disease and β-thalassemia.

NSC 663284 (DA-3003-1) is a potent, cell-permeable, and irreversible Cdc25 dual specificity phosphatase inhibitor, has an IC₅₀ for Cdc25B2 of 0.21 μM. NSC 663284 exhibits mixed competitive kinetics against Cdc25A, Cdc25B(2), and Cdc25C with Ki values of 29, 95, and 89 nM, respectively. NSC 663284 inhibits NSD2 (IC₅₀ of 170 nM) through a direct interaction with the catalytic SET domain (K_d of 370 nM).

UNC3866 is a potent antagonist of the CBX7-H3 interaction as determined by AlphaScreen (IC₅₀=66±1.2 nM) and is more than 100-fold selective for CBX7 over the other nine members of this methyl-lysine (Kme) reader panel.

OTS186935 hydrochloride is a potent protein methyltransferase SUV39H2 inhibitor with an IC₅₀ of 6.49 nM. OTS186935 hydrochloride shows significant inhibition of tumor growth in mouse xenograft models without any detectable toxicity. OTS193320 hydrochloride regulates the production of γ-H2AX in cancer cells.

NSD-IN-2 is a potent and irreversible NSD inhibitor with inhibitory activity towards members of the NSD family (NSD1/2/3). NSD-IN-2 can be used in research of acute myeloid leukemia.