h3k9

SIRT6-IN-5(SIRT6 inhibitor 5) is a potent and selective SIRT6 inhibitor with an IC50 value of 34 μM.SIRT6-IN-5 is immunosuppressive and chemo-sensitizing, increases H3K9 acetylation and glucose uptake in cultured cells, and reduces T-cell proliferation.

Compound A5b, also known as JMJD3 HDAC-IN-1, is a dual inhibitor that targets both JMJD3 (Jumonji domain-containing protein demethylase 3) and HADC1 (histone deacetylase, IC50 = 16 nM). It induces hypermethylation of histone H3K27 and hyperacetylation of H3K9, while also promoting apoptosis through the cleavage of caspase-7 and PARP. This compound has demonstrated the ability to effectively inhibit cancer cell cloning, migration, and invasion [1].

Bomedemstat (IMG-7289) hydrochloride is an orally active, irreversible inhibitor of lysine-specific demethylase 1 (LSD1), exhibiting anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis.

CMS-121, a quinolone derivative, is an orally active acetyl-CoA carboxylase 1 (ACC1) inhibitor. CMS-121 protects HT22 cells against ischemia and oxidative damage (EC50: 7 nM and 200 nM). CMS-121 shows strong neuroprotective, antioxidative, anti-inflammatory, and renoprotective activities.

BRD9539 is an inhibitor of euchromatin histone methyltransferase 2 (EHMT2), also known as G9a, with an IC50 value of 6.3 μM

BML-278 is a SIRT1 activator with an EC150 of 1 μM. It increases H3K9 methylation and inhibits H3K9 acetylation in parental and maternal prokaryotes, improving early embryonic development. BML-278 induces cell cycle arrest at the G1 S phase in primary human mesenchymal stromal cells, delaying senescence. It also reduces microtubule protein acetylation in U937 cells and increases mitochondrial density in mouse C2C12 myoblasts.

HDAC1 6-IN-1 is a potent multi-target inhibitor of GLP (IC50: 1.3 nM), HDAC6 (IC50: 13 nM) and HDAC1 (IC50: 89 nM). HDAC1 6-IN-1 inhibits the methylation and deacetylation of H3K9 at the protein level. HDAC1 6-IN-1 can block the cell cycle of cancer cells in G0 G1 phase, induce apoptosis and prevent cancer cell migration and invasion.

S2157, a potent N-alkylated tranylcypromine (TCP) derivative lysine-specific demethylase 1 (LSD1) inhibitor, enhances H3K9 methylation and concurrently reduces H3K27 acetylation at super-enhancer sites. This compound triggers apoptosis in TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells by inhibiting NOTCH3 and TAL1 gene expression. Moreover, S2157 is capable of crossing the blood-brain barrier, effectively eliminating central nervous system (CNS) leukemia in mice models implanted with T-ALL cells.

HDAC3-IN-2 (compound 4i), a pyrazinyl hydrazide-based HDAC3 inhibitor with an IC50 of 14 nM, effectively targets triple-negative breast cancer cells. Demonstrating cytotoxic activity, HDAC3-IN-2 exhibits an IC50 of 0.55 μM against 4T1 cells and 0.74 μM against MDA-MB-231 cells. In vivo, it shows anti-tumor efficacy in tumor-bearing mouse models by selectively elevating acetylation of histones H3K9, H3K27, and H4K12, enhancing apoptosis-inducing proteins caspase-3, caspase-7, and cytochrome c, and diminishing proliferation markers Bcl-2, CD44, EGFR, and Ki-67 [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.

E67-2, a derivative of E67, is a low-toxicity, selective inhibitor of the KIAA1718 Jumonji domain. It has an IC 50 value of 3.4 μM. E67-2 specifically inhibits the Jumonji demethylase for histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) demethylase.

S2116 is a powerful inhibitor of lysine-specific demethylase 1 (LSD1), and it is a derivative of N-alkylated tranylcypromine (TCP). S2116 exhibits its inhibitory effects by increasing H3K9 methylation and inducing reciprocal H3K27 deacetylation at super-enhancer regions. In TCP-resistant T-cell acute lymphoblastic leukemia (T-ALL) cells, S2116 triggers apoptosis by repressing the transcription of NOTCH3 and TAL1 genes. Furthermore, S2116 demonstrates significant growth retardation of T-ALL cells when xenotransplanted into mice.

BRD6688 is a selective HDAC2 inhibitor that acts by enhancing the learning and memory processes

BRD4770, a histone methyltransferase G9a inhibitor, induces cell senescence.

OSS_128167 (SIRT6-IN-1) is a specific SIRT6 inhibitor, and for SIRT6(IC50=89 μM), SIRT1(IC50=1578 μM) and SIRT2(IC50=751 μM).

INCB059872, also known as INCB59872, is a potent, selective, and orally active lysine-specific demethylase 1 inhibitor. INCB059872 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively, through amine oxidation. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes.

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.

ML324(IC50=920 nM) is a specific inhibitor of jumonji histone demethylase (JMJD2).