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.

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.

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].

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.

HDAC-IN-83 (compound 9D) is an inhibitor of histone deacetylase (HDAC), demonstrating an IC50 of 0.01 μM for HDAC1 and 0.44 μM for HDAC6. It exhibits anticancer and antiproliferative activities and promotes caspase-3 7 activation. The compound inhibits Cal27, HepG2, and MRC-5 cells with IC50 values of 0.693 μM, 0.427 μM, and 3.19 μM, respectively.

Fimepinostat (CUDC 907) is an orally bioavailable inhibitor of both phosphoinositide 3-kinase (PI3K) class I and pan-histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. Upon oral administration, CUDC-907 inhibits the activity of both PI3K class I isoforms and HDAC, thereby preventing the activation of the PI3K-AKT-mTOR signal transduction pathway that is often overactivated in many cancer cell types.

HDAC3-IN-T247 (HDAC3 inhibitor T247) is a selective and potent histone deacetylase 3 (HDAC3) inhibitor with anticancer and antiviral activities.HDAC3-IN-T247 induces NF-κB acetylation in human colon cancer HCT116 cells in a dose-dependent manner.HDAC3-IN-T247 inhibits cancer cell proliferation. HDAC3-IN-T247 inhibits cancer cell proliferation.

HDAC3-IN-T326 is a potent and selective HDAC3 inhibitor that acts by increasing NF-κB acetylation and activating HIV gene expression in latent HIV-infected cells.

Suberoylanilide hydroxamic acid (SAHA) is a class I and class II histone deacetylase (HDAC) inhibitor that binds directly to the catalytic site of the enzyme thereby blocking substrate access. SAHA-BPyne is a SAHA derivative with a benzophenone crosslinker and an alkyne tag intended to be used for profiling HDAC activities in proteomes and live cells. Such terminal alkyne groups can be used in linking reactions, known as click chemistry, characterized by high dependability and specificity of azide-alkyne bioconjugation reactions. SAHA-BPyne labels HDAC complex proteins both in proteomes at 100 nM and in live cells at 500 nM and demonstrates an IC50 value of ~3 μM for inhibition of HDAC activity in HeLa cell nuclear lysates in an HDAC activity assay.

CAY10722 is an inhibitor of sirtuin 3 (SIRT3), a class III HDAC (71% inhibition at 200 μM). SIRT3 is involved in modulating metabolic homeostasis as a NAD+-dependent protein deacetylase in the mitochondria. SIRT3 functions as either an oncogene or tumor suppressor, depending on cancer cell type. High SIRT3 expression in patient-derived esophageal cancer tissues is associated with shorter survival and, in mice, downregulation leads to a lower tumor load. In contrast, low SIRT3 expression in patient-derived breast cancer cells is correlated with shorter survival.

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

HDAC1/2-IN-3 is an inhibitor of both HDAC1 and HDAC2, demonstrating IC50 values of 0-5 nM and 5-10 nM, respectively.

Theophylline (1,3-Dimethylxanthine) sodium glycinate is a potent phosphodiesterase (PDE) inhibitor that targets PDE3 to relax airway smooth muscle and is used in asthma and chronic obstructive pulmonary disease (COPD) research. It also functions as an adenosine receptor antagonist, histone deacetylase (HDAC) activator, and exhibits anti-inflammatory activity by increasing IL-10 levels and inhibiting NF-κB nuclear import, while inducing apoptosis [1] [2] [3] [4] [5].

HDAC-IN-27 is a potent and orally active inhibitor of HDAC Class I (0.43 nM - 3.01 nM for HDAC1-3). HDAC-IN-27 shows activity against anti-acute myeloid leukemia (AML).