g9a/glp

MS8511 HCl is a selective and potent covalent inhibitor of G9a GLP that acts by targeting cysteine residues in the substrate binding site. MS8511 has anticancer activity and antiproliferative activity and reduces intracellular H3K9me2 levels.MS8511 can be used to study a wide range of cancers including brain, breast, and ovarian cancers .

MS0124 is a potent and selective G9A-like protein (GLP) inhibitor with IC50 values of 13±4 nM and 440±63 nM, respectively.

MS8511, a selective covalent irreversible inhibitor of G9a GLP, targets a cysteine residue at the substrate binding site, displaying IC50 values of 100 nM (G9a) and 140 nM (GLP), alongside Kd values of 44 nM (G9a) and 46 nM (GLP). This compound effectively reduces cellular H3K9me2 levels and boosts antiproliferation activity, making it applicable in cancer research involving brain, breast, ovarian, lung, bladder, melanoma, and colorectal cancers, as well as studies on Alzheimer's disease (AD), sickle cell disease, and Prader−Willi syndrome (PWS) [1].

A-366 is a highly selective peptide-competitive histone methyltransferase G9a inhibitor with IC50s of 3.3 and 38 nM for G9a and GLP, respectively.It is more than 1,000-fold selective for G9a and GLP over the other 21 methyltransferases. It is an inhibitor of the Spindlin1-H3K4me3 interaction with an IC50 of 182.6 nM.It exhibits high affinity for human H3R with a Ki value of 17 nM, and shows subtype selectivity between subgroups of the histaminergic and dopaminergic receptor families.

UNC0638 is an inhibitor of β-protein lysine methyltransferases G9a(IC50<15 nM) and GLP(IC50=19 nM) with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets.

BIX-01294 trihydrochloride is an inhibitor of G9a histone methyltransferase.In a cell-free assay, the IC50=2.7 μM for G9a histone methyltransferase.

W4022 (compound 16) is an efficient dual inhibitor of the lysine methyltransferases G9a NSD2, with IC50 values of 0.241 μM for G9a and 0.017 μM for NSD2. It exhibits potent antiproliferative properties, including the ability to suppress colony formation, induce apoptosis, and inhibit metastasis of cancer cells. W4022 effectively curtails the catalytic activities of G9a and NSD2 within cells and demonstrates significant antitumor efficacy in PANC-1 xenograft models.

G9D-4 is an effective degrader of G9a with a DC50 value of 0.1 μM in PANC-1 cells, and it does not directly interfere with GLP proteins (DC50 greater than 10 μM). This compound plays a significant role in pancreatic cancer research.

MS-8709 is a G9a GLP PROTAC Degrader (DC50(G9a) = 274 nM; DC50(GLP) = 260 nM) that induces G9a GLP degradation in a concentration-, time-, and ubiquitin-proteasome system (UPS)-dependent manner. It shows higher selectivity for G9a GLP over other methyltransferases, without affecting G9a GLP mRNA expression. In addition, MS-8709 demonstrates superior inhibition of prostate cancer, leukemia, and lung cancer cell growth compared to its parent compound, the G9a GLP inhibitor UNC0642, and possesses favorable murine pharmacokinetic properties for in vivo efficacy studies.

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.

BIX-01294 is an G9a Histone Methyltransferase inhibitor(IC50 : 1.9 μM).

DS79932728 is an orally active inhibitor of G9a and GLP, with IC50 values of 12.6 nM and 75.7 nM, respectively. It induces the production of γ-globin, thereby increasing fetal hemoglobin (HbF) levels. In cynomolgus monkey models, DS79932728 enhances the proportion of F-reticulocytes (F-rets) and shows good oral absorption characteristics.

UNC0638 hydrate selectively inhibits G9a and GLP histone methyltransferases with IC50 values of 15 nM and 19 nM, respectively. It is effective in inhibiting invasion and migration of TNBC cells in vitro. Additionally, UNC0638 hydrate acts as an inhibitor of EHMT1 2 and induces the expression of fetal hemoglobin (HbF) in cultures of human erythroid progenitor cells. Furthermore, it exhibits antiviral activity against FMDV (foot-and-mouth disease virus) and VSV (vesicular stomatitis virus), demonstrating remarkable potency and selectivity across various epigenetic and non-epigenetic targets.

CM-272 is a dual G9a DNA methyltransferases (DNMTs) inhibitor.

Antitumor agent-101 is a selective, covalent inhibitor targeting lysine methyltransferases G9a GLP, demonstrating IC50 values of 8.5 nM for G9a and 5.5 nM for GLP. It exhibits antitumor efficacy in the PANC-1 xenograft model [1].

UNC0321 is an effective inhibitor of histone methyltransferase G9a with a Ki of 63 pM and with IC50s 9 nM and 6 nM in ECSD and CLOT assays. UNC0321 inhibits GLP with IC50s of 15 nM and 23 nM in ECSD and CLOT assays.

UNC0646 is a potent and selective inhibitor of the homologous protein lysine methyltransferases G9a and GLP (IC50s: 6 nM 15 nM for G9a GLP). UNC0646(UNC 0646) potently blocks G9a GLP methyltransferase activity in cells (IC50: 10 nM in MCF7 cells) and exhibits low cellular toxicity (EC50: 4.7 μM in MCF7 cells).

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.

MS012 is a Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase (Kd = 46 ± 15 nM).

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].

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.

UNC0642 is an effective and specific G9a GLP inhibitor (IC50< 2.5 nM).

MS8511 (hydrochloride) is a specific covalent and irreversible inhibitor of G9a GLP, targeting the cysteine residue at the substrate binding site. It has an IC50 of 100 nM for G9a and 140 nM for GLP, with Kd values of 44 nM for G9a and 46 nM for GLP. This compound reduces intracellular H3K9me2 levels and enhances antiproliferative activity, making it useful for studying various cancers, including brain, breast, ovarian, lung, bladder cancers, melanoma, and colorectal cancer, as well as other diseases like Alzheimer's disease (AD), sickle cell disease, and Prader-Willi syndrome (PWS).