histone deacetylases

Tasquinimod (ABR-215050) is an oral antiangiogenic agent with potential antitumor activity. It is also an S100A9 inhibitor and binds to the HDAC4Zn2+ binding structural domain with Kd values between 10 and 30 nM.

MPI_5a is an effective and selective inhibitor of HDAC6 (IC50=36 nM). MPI_5a weakly inhibits other HDAC isoforms and it also inhibits acyl-tubulin accumulation in cells (IC50: 210 nM).

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.

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.

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

Valproic Acid (2-Propylpentanoic Acid) is an HDAC inhibitor that inhibits HDAC1 activity, induces HDAC2 degradation, and is orally active. Valproic Acid can be used in epilepsy and bipolar disorder research.

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.

Belinostat (PXD101) is an inhibitor of hydroxamic acid-type histone deacetylase (HDAC, IC50 of 27 nM in HeLa cell extracts),and with antineoplastic activity.

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.

Divalproex Sodium (Valproate semisodium) binds to and inhibits gamma-aminobutyric acid (GABA) transaminase and its anticonvulsant activity may be exerted by increasing brain concentration of GABA and by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. It also is an HDAC inhibitor, Comprised of sodium valproate and valproic acid with anticonvulsant and antiepileptic activities. Divalproex may also work by suppressing repetitive neuronal firing through the inhibition of voltage-sensitive sodium channels.

Bufexamac (Bufexamic acid) is a COX inhibitor for IFN-α release with anti-inflammatory, analgesic, and antipyretic action.

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.

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.

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.

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.

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.

Ricolinostat (Rocilinostat) is an orally bioavailable, specific inhibitor of histone deacetylase 6 (HDAC6) with potential antineoplastic activity.

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

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

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

Entinostat (MS-275) is an HDAC class I selective inhibitor of HDAC1, HDAC2 and HDAC3 (IC50=243 453 248 nM) with oral activity. Entinostat has antitumor activity.

Nexturastat A is an effective and specific HDAC6 inhibitor (IC50: 5 nM). Its selectivity is >190-fold than other HDACs.