HDAC

Tasquinimod (ABR-215050) is a quinoline-3-carboxamide linomide analog with antiangiogenic and potential antineoplastic activities. Tasquinimod has been shown to decrease blood vessel density but the exact mechanism of action is not known. This agent has also been shown to augment the antineoplastic effects of docetaxel and androgen ablation in a murine model of prostate cancer involving human prostate cancer xenografts.

Curcumin (Natural Yellow 3) is a phenolic natural product, an inhibitor of histone acetyltransferase p300/CREB (IC50=25 μM) with specificity. Curcumin has a wide range of pharmacological activities such as antitumor, anti-inflammatory and antioxidant.

Romidepsin (FR 901228) is an HDAC inhibitor that inhibits HDAC1/2/4/6 (IC50=36/47/510/1400 nM). Romidepsin has antitumor activity and can be used for the treatment of peripheral T-cell lymphoma and cutaneous T-cell lymphoma.

Tucidinostat (Chidamide) is an effective and orally bioavailable HDAC enzymes class I (HDAC1/2/3) and class IIb (HDAC10) inhibitor, with IC50s of 95, 160, 67 and 78 nM, less active on HDAC8/11 (IC50: 733/432 nM), and shows no effect on HDAC4/5/6/7/9.

Trichostatin A (TSA) is a natural derivative of diene isohydroxamic acids. Trichostatin A is a histone deacetylase inhibitor (IC50=1.8 nM) that is reversible and specific. Trichostatin A leads to the hyperacetylation of core histones, which regulates chromatin structure.

Theophylline monohydrate (Quibron) appears to inhibit phosphodiesterase and prostaglandin production, regulate calcium flux and intracellular calcium distribution, and antagonize adenosine. Theophylline monohydrate is a natural alkaloid derivative of xanthine isolated from the plants Camellia sinensis and Coffea arabica. Physiologically, this agent relaxes the bronchial smooth muscle, produces vasodilation (except in cerebral vessels), stimulates the CNS, stimulates the cardiac muscle, induces diuresis, and increases gastric acid secretion; it may also suppress inflammation and improve contractility of the diaphragm.

Valproic acid sodium salt (Sodium Valproate) is the sodium salt form of valproic acid with anti-epileptic activity. Valproic acid sodium salt is converted into its active form, valproate ion, in blood. Although the mechanism of action remains to be elucidated, Valproic acid sodium salt increases concentrations of gamma-aminobutyric acid (GABA) in the brain, probably due to inhibition of the enzymes responsible for the catabolism of GABA. This potentiates the synaptic actions of GABA. Valproic acid sodium salt may also affect potassium channels, thereby creating a direct membrane-stabilizing effect.

Panobinostat (NVP-LBH589) is a broad-spectrum HDAC inhibitor (IC50=5 nM) with oral activity and non-selectivity. Panobinostat has antitumor activity and induces apoptosis and autophagy.

mTOR/HDAC-IN-1 HCl is a potent dual inhibitor of mTOR and HDAC with potential anti-inflammatory, anti-proliferative, autophagy and apoptosis-inducing effects for cancer research.

4-Phenylbutyric acid (Benzenebutyric acid) is an inhibitor of HDAC,and is an antineoplastic agent.

Exifone (NSC-680919) is a mixed, nonessential activator of HDAC1 that is capable of binding to both free and substrate-bound enzyme, resulting in an increased relative maximal rate of HDAC1-catalyzed deacetylation.

Sodium 4-phenylbutyrate (TriButyrate), a transcriptional regulator, reversibly inhibits class I and II histone deacetylases (HDACs )resulting in a global increase in gene expression, decreased cellular proliferation, increased cell differentiation, and the induction of apoptosis in susceptible tumor cell populations.

HDAC-IN-7 (HBI-8000) (Chidamide impurity) is an impurity of Chidamide. Chidamide is a potent and orally bioavailable inhibitor of HDAC enzymes class I (HDAC1 2 3) and class IIb (HDAC10).

HDAC8-IN-20a (HDAC8 inhibitor-20a) is a potent and selective HDAC8 inhibitor with an IC50 of 27 nM. HDAC8-IN-20a blocks activation of growth receptor survival signals.

HDAC-IN-52 is a pyridine-containing HDAC inhibitor that inhibits HDAC1, HDAC2, HDAC3 and HDAC10 with IC50s of 0.189, 0.227, 0.440 and 0.446 μM, respectively. HDAC-IN-52 can be used in cancer research.

HDAC6 degrader 9c is a small molecule histone deacetylase 6 (HDAC6) degrader that can be used to study cancer or other diseases.

Homobutein (3-O-Methylbutein) is a dual inhibitor of HDACs and NF-κB with IC50s of 190 and 38 μM. Homobutein is an iron chelator with anticancer, anti-inflammatory, antiparasite, and antioxidation activities.

BRD4097, a negative control in the HDAC1/2/3/8 assay, is a selective histone deacetylase (HDAC3) inhibitor that can be used to protect b-cells and improve insulin resistance, help promote cognitive function and enhance learning and memory formation.

HDAC-IN-57 is an orally active pan-inhibitor of histone deacetylase (HDAC), inhibiting HDAC1, HDAC2, HDAC6, and HDAC8 with IC50 values of 2.07 nM, 4.71 nM, 2.4 nM, and 107 nM, respectively. HDAC-IN-57 inhibits LSD1 with an IC50 value of 1.34 μΜ. HDAC-IN-57 has anti-tumor activity and can induce apoptosis.

BRD 9757 (N-Hydroxy-1-cyclopentene-1-carboxamide) is a selective inhibitor of HDAC6 (IC50 = 30 nM).

MC2590 is a potent and selective histone deacetylase (HDAC) inhibitor that inhibits HDAC1-3, -6, -8, and -10 activities, induces cell cycle arrest, and promotes apoptosis.

HDAC-IN-51 is an HDAC inhibitor.

Givinostat hydrochloride (ITF2357 hydrochloride) is an inhibitor of HDAC with IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride exhibits anti-inflammatory, anti-angiogenic, and antineoplastic activities.

ACY-957 (HDAC Inhibitor C001) is an orally active and selective inhibitor of HDAC1 and HDAC2 (IC50s: 7 nM, 18 nM, and 1300 nM against HDAC1/2/3) and shows no inhibition on HDAC4/5/6/7/8/9.

Corin is an irreversible inhibitor of HDAC1(IC50 = 147 nM) and LSD1(Ki = 110 nM).

CRA-026440 hydrochloride is a potent and broad-spectrum HDAC inhibitor. CRA-026440 hydrochloride exhibits Ki values against recombinant HDAC isoenzymes HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are 4 nM, 14 nM, 11 nM, 15 nM, 7 nM, and 20 nM, respectively. CRA-026440 hydrochloride exhibits antitumor and antiangiogenic activities.

ACY-1083 is a selective and brain-penetrating HDAC6 inhibitor (IC50: 3 nM) and effectively reverses chemotherapy-induced peripheral neuropathy.

SS-208 is a selective inhibitor of HDAC6 (IC50 = 12 nM) with anti-tumor activity. SS-208 shows selectivity over other HDAC subtypes.

Crebinostat is a potent histone deacetylase (HDAC) inhibitor, inhibiting HDAC1, HDAC2, HDAC3, and HDAC6 with IC50s of 0.7 nM, 1.0 nM, 2.0 nM, and 9.3 nM, respectively.Crebinostat increases the density of synapsin-1 punctae along dendrites in neurons in vitro. Crebinostat increased the density of synapsin-1 punctae along dendrites in neurons in vitro. crebinostat modulated chromatin-mediated neuroplasticity and enhanced memory in mice. crebinostat induced histone H3 and histone H4 acetylation and enhanced the expression of the cAMP-responsive element binding protein (CREB) target gene, Egr1. Crebinostat induces histone H3 and histone H4 acetylation and enhances the expression of Egr1, a cAMP response element binding protein (CREB) target.

CM-675 is a dual inhibitor of phosphodiesterase 5 (PDE5) and class I histone deacetylases (IC50s: 114 nM and 673 nM for PDE5 and HDAC1) with the potential to treat Alzheimer’s disease.

MPT0G211 is a highly selective and orally active HDAC6 inhibitor (IC50=0.291 nM) that has neuroprotective effects and has shown anti-metastatic activity in human breast cancer cells. MPT0G211 has 1,000 times more affinity for HDAC6 than other HDAC subtypes. MPT0G211 can cross the blood-brain barrier and could be used to improve tau phosphorylation and cognitive deficits in Alzheimer's disease models.

Patamostat (E-3123) mesylate is a histone deacetylase (HDAC) inhibitor.Patamostat mesylate increases the accumulation of acetylated histones and microtubule proteins in tumor cells, contributing to cell cycle termination and apoptosis.Patamostat mesylate has antitumor activity and can be used in the study of multiple myeloma.

HDAC-IN-4 is a selective HDAC6 and HDAC10 inhibitor (pIC50s: 7.2 and 6.8 in BRET assay) with antitumoral activity.

Sinapinic Acid (Synapoic acid) protects the rat liver from CCl4-induced inflammation, most likely by acting as a free radical scavenger and modulator of NF-κB p65 activation and proinflammatory cytokine expression. Sinapic acid with antioxidant role protects cardiac cells and its functions from I/R induced oxidative stress. Sinapic acid is a potentially useful agent for the protection against liver fibrosis and cirrhosis. Sinapic acid prevents the alterations in the levels of lipids and lipoproteins by virtue of its anti-lipidaemic effect in isoproterenol induced myocardial infarcted rats. Sinapic acid ameliorates hyperglycemia through PLC-PKC signals to enhance the glucose utilization in diabetic rats.

PTACH (Cpd 51) (NCH-51) is a SAHA-based inhibitor of human HDAC. It can potently inhibit the growth of various human Y cells (EC50: 1 to 10 μM).

TMP195 (TFMO 2) is a selective class IIa histone deacetylase (HDAC) inhibitor.

Rac-Belinostat (PX-105684) is a novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase.

Scriptaid (GCK1026) is an inhibitor of HDAC, and has a greater effect on acetylated H4 than H3.

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.

Vorinostat (SAHA) is a pan-histone deacetylase (HDAC) inhibitor (IC50=10 nM) with inhibitory activity against HDAC1/2/3/6/7/11. Vorinostat has antitumor activity, induces cell differentiation, blocks the cell cycle and induces apoptosis.

Mocetinostat (MG0103) is an orally available HDAC inhibitor with most potency for HDAC1 (IC50: 0.15 μM), 2- to 10- fold selectivity against HDAC2 3 11.

ACY-738 demonstrates inhibitory activity against recombinant HDAC6 (IC50: 1.7 nM), with respective average selectivity over class I HDACs being 100-fold.

Pyroxamide is an histone deacetylases (HDACs) inhibitor with antineoplastic properties ( HDAC1;IC50: 0.1-0.2 μM).

Entinostat (MS-275) (MS-275) is an inhibitor of HDACs that inhibits HDAC1 and HDAC3 (IC50s: 0.18 0.74 μM).

SantacruzaMate A (CAY-10683) is a potent and selective HDAC inhibitor.

AR42 (OSU-HDAC42) is an HDAC inhibitor (IC50: 30 nM).

Tubastatin A Hydrochloride (TSA HCl) is an effective and specific HDAC6 inhibitor (IC50: 15 nM). It has selectivity (>1000-fold) against all other isozymes except HDAC8 (>57-fold).

Quisinostat (JNJ-26481585) (JNJ-26481585) is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7.

NSC 3852 is a potent inhibitor of histone deacetylase.

Tubacin is a highly potent and selective, reversible, cell-permeable HDAC6 inhibitor with an IC50 of 4 nM, approximately 350-fold selectivity over HDAC1.