HDAC3 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.

TNG260 is a selective, orally effective inhibitor of HDAC1 and CoREST complex, with a 10-fold selectivity for HDAC1 over HDAC3 and a 500-fold selectivity for CoREST complex over NuRD and Sin3 complex. TNG260 reshapes the tumor immune microenvironment, reduces immunosuppressive neutrophil infiltration, promotes effector T cell recruitment, and reverses anti-PD-1 resistance caused by STK11 deficiency by inhibiting the activity of the CoREST-HDAC1 complex. TNG260 induces durable tumor regression in combination with α-PD1 in MC38 tumor-bearing mice with STK11 mutations, and has lower toxicity to bone marrow cells than non-selective HDAC inhibitors.

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.

Zabadinostat (CXD101) is a potent, selective and orally active class I HDAC inhibitor with IC₅₀s of 63 nM, 570 nM and 550 nM for HDAC1, HDAC2 and HDAC3, respectively. Zabadinostat has no activity against HDAC class II. Zabadinostat has antitumor activity.

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.

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).

Domatinostat (4SC-202 free base) is a selective class I HDAC inhibitor with IC₅₀ of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. It also displays inhibitory activity against Lysine specific demethylase 1 (LSD1).

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-957 is an orally active and selective inhibitor of HDAC1 and HDAC2, with IC₅₀s of 7 nM, 18 nM, and 1300 nM against HDAC1/2/3, respectively, and shows no inhibition on HDAC4/5/6/7/8/9.

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).

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.

Nanatinostat (CHR-3996) is a potent, class I selective and orally active HDAC inhibitor with IC₅₀s of 3 nM, 4 nM, and 7 nM for HDAC1, HDAC2, and HDAC3, respectively. Nanatinostat has low activity against HDAC5 (IC₅₀ of 200 nM) and HDAC6 (IC₅₀ of 2100 nM). Nanatinostat induces apoptosis in myeloma cells. Nanatinostat has potent anticancer effects, such as myeloma, advanced solid tumours and colorectal cancer.

BRD4884 is a potent and brain-penetrant HDAC inhibitor with IC₅₀ values of 29 nM, 62 nM, and 1090 nM for HDAC1, HDAC2, and HDAC3, respectively. BRD4884 can be used for the study of cognitive impairment.