hdac-in-3

HDAC-IN-3 (GSK3117391A) is a potent histone deacetylase (HDAC) inhibitor, and treatment chronic inflammatory disorders.

Top HDAC-IN-3 (Compound 31) is a dual inhibitor of Topoisomerase and HDAC with oral activity. It induces DNA damage by elevating reactive oxygen species (ROS) levels, consequently inhibiting the clonal formation and migration of cancer cells, and triggering apoptosis (Apoptosis) and cell cycle arrest. Top HDAC-IN-3 demonstrates a significant antitumor effect in NSCLC models, exhibiting a tumor growth inhibition (TGI = 77.5%, 100 mg kg) superior to that of the HDAC inhibitor SAHA and the combination of SAHA with the topoisomerase inhibitor Irinotecan.

c-Met HDAC-IN-3, a dual inhibitor targeting both c-Met and HDAC, exhibits potent inhibitory activity with IC50 values of 12.50 nM for c-Met and 26.97 nM for HDAC1. It induces apoptosis and causes cell cycle arrest in the G2 M phase.

Tubulin HDAC-IN-3 (compound 12a) is a potent dual inhibitor of tubulin polymerization and HDAC1 8, with IC50 values of 5.4 μM for tubulin polymerization, and 0.155 and 0.177 μM for HDAC1 and HDAC8, respectively. It obstructs the cell cycle, triggers apoptosis, and suppresses colony formation [1].

CDK HDAC-IN-3 is an orally active dual inhibitor of HDACs and CDKs, offering potent and selective inhibition of CDK9, CDK12, CDK13, HDAC1, HDAC2, and HDAC3, with IC50 values of 98.32 nM, 98.85 nM, 100 nM, 62.12 nM, 93.28 nM, and 82.87 nM, respectively, and is applicable in the treatment of acute myeloid leukemia (AML) [1].

JAK HDAC-IN-3 (13a), a dual inhibitor of JAK and HDAC, exhibits IC50 values of 25.36 nM for JAK2, 0.2 μM for HDAC, and 0.43 μM for HDAC1, respectively [1].

PI3K HDAC-IN-3 (36) acts as a dual inhibitor targeting PI3K and HDAC, exhibiting respective IC50 concentrations of 0.23 nM for PI3Kα and 172 nM for HDAC1. In MV4-11 cells, it inhibits AKT phosphorylation while enhancing H3 acetylation. Furthermore, PI3K HDAC-IN-3 (36) demonstrates substantial, dose-dependent anticancer effects in an MV4-11 xenograft model [1].

HDAC-IN-38 is a potent inhibitor of HDAC. HDAC-IN-38 has similar micromolar inhibitory effects on HDAC1, 2, 3, 5, 6 and 8, and also increases histone acetylation levels (H3K14 or H4K5). HDAC-IN-38 increases cerebral blood flow (CBF), reduces cognitive impairment and improves hippocampal atrophy.

HDAC HSP90-IN-3 is a selective and potent dual inhibitor of fungal Hsp90 (IC50: 0.83 μM) and HDAC (IC50: 0.91 μM), exhibiting antifungal effects against azole-resistant Candida albicans. HDAC HSP90-IN-3 exhibits inhibitory effects on important virulence factors and is able to downregulate the resistance genes ERG11 and CDR1.

HDAC-IN-32 is a highly effective HDAC inhibitor presenting IC50 values of 5.2, 11, and 28 nM for HDAC1, HDAC2, and HDAC6, respectively. This compound demonstrates notable anti-proliferative properties against tumor cells, as well as significant in vivo antitumor efficacy, which can elicit antitumor immunity [1].

HDAC-IN-33 is a highly potent HDAC inhibitor, effectively inhibiting HDAC1, HDAC2, and HDAC6 with IC50 values of 24, 46, and 47 nM, respectively. This compound demonstrates significant antiproliferation activity against tumor cells and exhibits remarkable in vivo antitumor efficacy. Additionally, HDAC-IN-33 initiates the activation of antitumor immunity [1].

HDAC-IN-35 (Compound 14) is a potent and selective inhibitor of VEGFR-2 and HDAC, exhibiting IC50 values of 13.2 μM for VEGFR-2 and 0.166 μM for HDAC6.

HDAC-IN-30 is a multi-target HDAC inhibitor. HDAC-IN-30 inhibits HDAC1 (IC50 =13.4 nM), HDAC2 (IC50 =28.0 nM), HDAC3 (IC50 =9.18 nM), HDAC6 (IC50 =42.7 nM), HDAC8 (IC50 =131 nM). HDAC-IN-30 shows potent antitumor efficacy.

HDAC-IN-31 is a selective, potent, orally active HDAC inhibitor that acts on HDAC1 (IC50: 84.90 nM), HDAC2 (IC50: 168.0 nM), HDAC3 (IC50: 442.7 nM), HDAC8 (IC50>10000 nM). HDAC-IN-31 has good anti-tumour effects. HDAC-IN-31 has shown potential research value in diffuse large B-cell lymphoma.

HDAC-IN-34 (compound 27) is a potent inhibitor of HDAC, targeting HDAC1 (IC50: 0.022 μM) and HDAC6 (IC50: 0.45 μM). It can bind to DNA and induce DNA damage, exhibiting a significant anti-proliferative effect on HCT-116 cells (IC50: 1.41 μM).

HDAC-IN-37 is a potent inhibitor of HDAC, targeting HDAC1 (IC50: 0.0551 μM), HDAC3 (IC50: 1.24 μM), HDAC8 (IC50: 0.948 μM), and HDAC6 (IC50: 34.2 μM). It slowly induces histone acetylation, prevents the transition from G1 to S phase, and induces early apoptosis.

HDAC-IN-39 is a potent inhibitor of HDAC and is able to act on HDAC1, HDAC2 and HDAC3 with IC50 values of 1.07 μM, 1.47 μM and 2.27 μM, respectively. HDAC-IN-39 induces cell cycle arrest in G2 M phase and also significantly inhibits microtubule polymerization. HDAC-IN-39 exhibits good anticancer effects on HDAC-IN-39 exhibited good anti-cancer effects on drug-resistant cancer cells.

HDAC-IN-36 is an orally active HDAC (histone deacetylase) inhibitor with an IC50 value of 11.68 nM for HDAC6. HDAC-IN-36 induces apoptosis, autophagy and inhibits migration. HDAC-IN-36 exhibits antitumor and antimetastatic effects and can be used to study breast cancer. HDAC-IN-36 exhibits antitumor and antimetastatic effects and can be used to study breast cancer.

mTOR HDAC-IN-1 (Compound 50) is a dual inhibitor of mTOR and HDAC, with IC50 values of 0.49 nM and 0.91 nM, respectively, holding potential as an anti-cancer agent [1].

MI-192 is a selective HDAC2 and HDAC3 inhibitor with IC50 values of 30 nM and 16 nM, respectively. It exhibits greater selectivity for HDAC2 3 over other HDAC isomers and induces apoptosis in myeloid leukemic cells, indicating potential therapeutic use in leukemia and as an anti-stroke agent [1] [2].

Nampt-IN-3 simultaneously inhibit nicotinamide phosphoribosyltransferase (NAMPT) and HDAC (IC50s of 31 nM and 55 nM, respectively).

FLT3 HDAC-IN-1 is a dual inhibitor targeting FLT3 and HDAC, with IC50 values of 30.4 nM for FLT3 and 52.4, 14.7 nM for HDAC1 3, respectively. It induces apoptosis in MV-4-11 cells and exhibits antiproliferative effects against BaF3 cells transformed by FLT3 mutations. FLT3 HDAC-IN-1 is useful for research on refractory solid tumors and hematological malignancies.

HDAC6-IN-49 (Compound 3) is an inhibitor of HDAC, with IC50 values of 0.012 and 0.735 µM against HDAC6 and HDAC1, respectively. Additionally, it inhibits MAO-B, cholinesterase (ChE), histamine receptor (H3R), and serotonin 6 receptor (5-HT6R). HDAC6-IN-49 exhibits neuroprotective effects in SH-SY5Y cells and enhances cognitive functions and motor abilities in fruit fly models of Parkinson's disease and C. elegans models of Alzheimer's disease.

ROCK HDAC-IN-1 (Compound 10h) serves as an orally effective inhibitor of ROCK HDAC. This compound suppresses ROCK1 2 (IC50: 254.9 nM, 58.18 nM) and HDAC1 2 3 6 8 (IC50: 9.09, 8.03, 6.26, 0.41, 7.69 nM). It stimulates the activation of DAMPs, notably calreticulin (CRT) exposure and HMGB1 release, suggesting its potential as an inducer of immunogenic cell death (ICD). ROCK HDAC-IN-1 exhibits antiproliferative effects against breast cancer cells (IC50: 0.37 μM for MDA-MB-231 cells), inhibits tumor growth, activates T cells, and shows no significant toxicity.