histone lysine methyltransferase

Bisubstrate inhibitor 78 is an inhibitor of nicotinamide N-methyltransferase (NNMT; IC50= 1.41 μM).1It binds the NNMT active site in the binding pockets for the NNMT substrates S-adenosyl-L-methionine (SAM) and nicotinamide . Bisubstrate inhibitor 78 is selective for NNMT over histone-lysine N-methytransferase NSD2 and protein arginine methyltransferase 1 (PRMT1; IC50s = >50 μM for both). It reduces levels of 1-methylnicotinamide in, and inhibits proliferation of, HSC-2 oral cancer cells when used at a concentration of 100 μM.This compound is unstable in powder form and other related salt forms are recommended.

UNC0379 is a selective, substrate-competitive inhibitor of the lysine methyltransferase (SETD8).

5WKS also known as ZINC97756584 is a biochemical. It is a G9a protein inhibitor.G9A/EHMT2 is a nuclear histone lysine methyltransferase that catalyzes H3K9me2, a reversible modification commonly associated with transcriptional gene silencing.5WKS can be used in the study of autoimmune diseases or tumors.

EML741 also inhibits DNMT1 (IC50, 3.1 μM), with no effect on DNMT3a or DNMT3b. EML741 exhibits low cell toxicity, and is membrane permeable and blood-brain barrier penetrated. EML741 is a histone lysine methyltransferase G9a GLP inhibitor, with an IC50 of 23 nM, Kd of 1.13 μM for G9a.

lutidinic acid (2,4-Dicarboxypyridine) is an in vitro and in cell inhibitor, as well as a known inhibitor of the histone lysine demethylases.

Histone H3 (1-21) is a truncated form of the Histone H3 protein consisting of amino acids 1 to 21. It serves as a common substrate for methyltransferase assays targeting Histone 3 at lysine 4 and lysine 9, as well as for acetyltransferase assays targeting Histone 3 at lysine 9 and lysine 14.

GSK-A is a Histone Lysine Methyltransferase EZH2 inhibitor.

MS2177 is a potent and selective inhibitor of SETD8, the only methyltransferase known to catalyze monomethylation of histone H4 lysine 20 (H4K20). MS2177 has an in vitro IC50 of 1.9 μM (σ = 1.05 μM, n = 4) in ascintillation proximity assay. Binding of MS2

PFI-2 hydrochloride ((R)-PFI-2 hydrochloride) is a potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 (IC50: 2 nM), 500 fold active than (S)-PFI-2.

The methylation of lysine residues on histones plays a central role in determining euchromatin structure and gene expression. The histone methyltransferase (HMTase) G9a can mono- or dimethylate lysine 9 on histone 3 (H3), contributing to early embryogenesis, genomic imprinting, and lymphocyte development. BIX01294 (hydrochloride hydrate) is a selective inhibitor of G9a HMTase (IC50 = 1.7 μM). It less effectively inhibits the HMTase G9a-like protein (GLP; IC50 = 38 μM) and has no effect on other known HMTases. BIX01294 has been used in combination with the calcium channel activator BayK8644 to facilitate the generation of induced pluripotent stem cells from somatic cells in vitro.

PFI-2 is an effective, specific and cell-active lysine methyltransferase SETD7 inhibitor (Ki IC50: 0.33 2 nM), 1000-fold selectivity over other methyltransferases and other non-epigenetic targets.

Histone H3 (21-44)-GK-biotin is a peptide fragment of histone H3 that corresponds to amino acid residues 22-45 of the human histone H3.1 and 3.2 sequences and is biotinylated via a C-terminal GK linker. Histone H3 (21-44) contains a lysine residue at position 23 that is subject to acetylation, an arginine at position 26 subject to methylation, and a serine at position 28 subject to phosphorylation, as well as lysine residues at positions 27 and 36 that are subject to methylation and acetylation. Histone H3 (21-44)-GK-biotin has been used as a substrate for the primate-specific histone methyltransferase PR domain-containing protein 7 (PRDM7) to determine substrate specificity.

SETD7-IN-1 (compound 7), a PFI-2 analogue, acts as both a substrate and inhibitor of histone lysine methyltransferase SETD7, exhibiting an inhibitory concentration (IC50) of 0.96 ± 0.10 µM [1].

TC-5115 is a potent inhibitor of MLL methyltransferase with IC50 value of 16 nM. TC-5115 may lead to the development of a new therapy for the treatment of human MLL leukemia. The mixed-lineage leukemia (MLL) protein, also known as MLL1, is a lysine methyltransferase specifically responsible for methylation of histone 3 lysine 4. MLL has been pursued as an attractive therapeutic target for the treatment of acute leukemia carrying the MLL fusion gene or MLL leukemia.

WM-3835 is a novel and high-specific small molecule inhibitor of Lysine Acetyltransferase 7 (KAT7, MYST2, HBO1) , able to potently suppressed OS cell proliferation and migration, and leads to apoptosis activation.

BIX-01338 hydrate is an inhibitor of histone lysine methyltransferase.

ZZM-1220, a covalent inhibitor of histone lysine methyltransferase G9a GLP, exhibits IC50 values of 458 nM for G9a and 924 nM for GLP. It effectively inhibits H3K9me2 in cells, induces apoptosis in triple-negative breast cancer (TNBC) cells, and arrests the cell cycle at the G2 M phase [1].

OTS193320, an imidazopyridine compound, acts as an inhibitor of SUV39H2 methyltransferase activity. It effectively reduces global histone H3 lysine 9 tri-methylation levels in breast cancer cells, promoting apoptotic cell death. When combined with Doxorubicin (DOX), OTS193320 enhances the reduction of γ-H2AX levels and decreases cancer cell viability more significantly than when either agent is used alone.

UNC0224 is a selective inhibitor of G9a with a Ki of 2.6 nM and IC50 of 15 nM. UNC0224 also potently inhibits GLP with assay-dependent IC50 values of 20-58 nM.