HDAC6 Inhibitor

Citarinostat (ACY241) is a second generation potent, orally active and high-selective HDAC6 inhibitor with an IC₅₀ of 2.6 nM (IC₅₀s of 35 nM, 45 nM, 46 nM and 137 nM for HDAC1, HDAC2, HDAC3 and HDAC8, respectively). Citarinostat has anticancer effects.

ACY-738 is a potent, selective and orally-bioavailable HDAC6 inhibitor, with an IC₅₀ of 1.7 nM; ACY-738 also inhibits HDAC1, HDAC2, and HDAC3, with IC₅₀s of 94, 128, and 218 nM.

Givinostat hydrochloride monohydrate (ITF-2357 hydrochloride monohydrate) is a HDAC inhibitor with an IC₅₀ of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat hydrochloride monohydrate can penetrate the blood-brain barrier (BBB).

Bufexamac is a selective Ⅱb HDAC (HDAC6, HDAC10) and LTA4H dual inhibitor, with K_ds of 0.53 µM and 0.22 µM for HDAC6 and HDAC10. Bufexamac is a nonsteroida anti-inflammatory drug.

CAY10603 (BML-281) is a potent and selective HDAC6 inhibitor, with an IC₅₀ of 2 pM; CAY10603 (BML-281) also inhibits HDAC1, HDAC2, HDAC3, HDAC8, HDAC10, with IC₅₀s of 271, 252, 0.42, 6851, 90.7 nM.

Quisinostat dihydrochloride (JNJ-26481585 dihydrochloride) is an orally active, potent pan-HDAC inhibitor with IC₅₀s of 0.11 nM, 0.33 nM, 0.64 nM, 0.46 nM, and 0.37 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11, respectively. Quisinostat dihydrochloride has a broad spectrum antitumoral activity. Quisinostat dihydrochloride can induce autophagy in neuroblastoma cells.

TYA-018 is an orally active, potent and highly selective HDAC6 inhibitor. TYA-018 can protect heart function in mice. TYA-018 also enhances energetics in mice by increasing expression of targets associated with fatty acid metabolism, protein metabolism, and oxidative phosphorylation.

SR-4370 is an inhibitor of HDAC, with IC₅₀s of 0.13 μM, 0.58 μM, 0.006 μM, 2.3 μM, and 3.4 μM for HDAC1, HDAC2, HDAC3, HDAC8, and HDAC6, respectively.

Crotonoside is isolated from Chinese medicinal herb, Croton. Crotonoside inhibits FLT3 and HDAC3/6, exhibits selective inhibition in acute myeloid leukemia (AML) cells. Crotonoside could be a promising new lead compound for the research of AML.

TH34, an HDAC6/8/10 inhibitor with IC₅₀s of 4.6 μM, 1.9 μM, and 7.7 μM respectively, shows high selectivity over HDAC1/2/3.

ACY-775 is a potent and selective inhibitor of the of histone deacetylase 6 (HDAC6) with an IC₅₀ of 7.5 nM. ACY775 also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2).

HDAC10-IN-1 (compound 13b) is a potent and highly selective HDAC10 inhibitor, with an IC₅₀ of 58 nM. HDAC10-IN-1 modulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.

Tinostamustine (EDO-S101) is a pan HDAC inhibitor; inhibits HDAC6, HDAC1, HDAC2 and HDAC3 with IC₅₀ values of 6 nM, 9 nM, 9 nM and 25 nM, respectively.

ACY-1083 is a selective and brain-penetrating HDAC6 inhibitor with an IC₅₀ of 3 nM and is 260-fold more selective for HDAC6 than all other classes of HDAC isoforms. ACY-1083 effectively reverses chemotherapy-induced peripheral neuropathy.

Droxinostat (NS 41080) is a histone deacetylase (HDAC) inhibitor. Droxinostat selectively inhibits HDAC3, HDAC6, and HDAC8 with IC₅₀ values of 16.9 μM, 2.47 μM, and 1.46 μM, respectively. Droxinostat can be used for the research of hepatocellular carcinoma (HCC).

T-518 is an orally active, BBB-penetrant and potent DFMO-based HDAC6 inhibitor with high selectivity (IC₅₀ = 36 nM). T-518 improves axonal transport. T-518 ameliorates object recognition deficit. T-518 can be studied in research for Alzheimer’s disease and tauopathy.

CHDI-390576, a potent, cell permeable and CNS penetrant class IIa histone deacetylase (HDAC) inhibitor with IC₅₀s of 54 nM, 60 nM, 31 nM, 50 nM for class IIa HDAC4, HDAC5, HDAC7, HDAC9, respectively, shows >500-fold selectivity over class I HDACs (1, 2, 3) and ~150-fold selectivity over HDAC8 and the class IIb HDAC6 isoform.

SW-100, a selective histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 2.3 nM, shows at least 1000-fold selectivity for HDAC6 relative to all other HDAC isozymes. SW-100 displays a significantly improved ability to cross the blood-brain-barrier.

Resminostat (RAS2410; 4SC-201) is a potent inhibitor of HDAC1, HDAC3 and HDAC6, with mean IC₅₀ values of 42.5, 50.1, 71.8 nM, respectively, and shows less potent activities against HDAC8, with an IC₅₀ of 877 nM.

SS-208 is a selective HDAC6 inhibitor, with an IC₅₀ of 12 nM. SS-208 possesses anti-tumor activity in melanoma.