HDAC8 Inhibitor

HDAC6-IN-4 (C10) is a potent, orally active and highly selective HDAC6 inhibitor with an IC₅₀ value of 23 nM. HDAC6-IN-4 induces cancer cells apoptosis and shows significant antitumor efficacy, without obvious toxicity.

CA/HDAC-IN-1 (Compound 11) is a CA and HDAC inhibitor with K_i values of 7.4 nM, 31.0 nM, and 7.3 nM for hCA II, hCA IX, and hCA XII, respectively, and IC₅₀ values of 0.21 μM and 3.60 μM for HDAC3 and HDAC8, respectively. CA/HDAC-IN-1 has anti-cancer activity against colon cancer, breast cancer, and melanoma.

HDAC6-IN-47 (Compound S-29b) is inhibitor for HDAC, which exhibits high affinities to HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, HDAC10 with K_i of 60, 56, 162, 0.44, 362 and 849 nM, respectively. HDAC6-IN-47 causes tubulin hyperacetylation in MV4-11, inhibits the proliferation of MV4-11 with an EC₅₀ of 0.50 µM. HDAC6-IN-47 can be used in research of leukemia.

GSK-3β/HDAC-IN-2 is a potent inhibitor of GSK-3β (IC₅₀ = 0.04 μM), HDAC2 (IC₅₀ = 1.05 μM, Ki = 0.070 μM) and HDAC6 (IC₅₀ = 1.52 μM, Ki = 0.017 μM). GSK-3β/HDAC-IN-2 inhibits HDAC2 and HDAC6 activities and blocks tau hyperphosphorylation. GSK-3β/HDAC-IN-2 exerts neuroprotective effects and shows no significant toxicity. GSK-3β/HDAC-IN-2 can be used in the research of Alzheimer's disease.

HDAC-IN-31 is a potent, selective and orally active HDAC inhibitor with IC₅₀s of 84.90, 168.0, 442.7, >10000 nM for HDAC1, HDAC2, HDAC3, HDAC8, respectively. HDAC-IN-31 induces apoptosis and cell cycle arrests at G2/M phase. HDAC-IN-31 shows good antitumor efficacy. HDAC-IN-31 has the potential for the research of diffuse large B-cell lymphoma.

JAK/HDAC-IN-2 is a potent 2-amino-4-phenylaminopyrimidine JAK/HDAC dual-target inhibitor. JAK/HDAC-IN-2 potently inhibits HDAC3/6 and JAK1/2 at nanomolar levels. JAK/HDAC-IN-2 has proapoptotic activity and inhibits histone deacetylation and STAT3 phosphorylation. JAK/HDAC-IN-2 presents remarkable antiproliferative activity in both hematological malignancies and solid cancers.

PIM-1/HDAC-IN-1 (compound 4d) is a PIM-1 inhibitor, with an IC₅₀ of 343.87 nM. PIM-1/HDAC-IN-1 has strong inhibitory activity and selectivity against HDAC 1 and HDAC 6, with IC₅₀ values of 63.65 and 62.39 nM, respectively. PIM-1/HDAC-IN-1 exhibits apoptosis inducing potential in MCF-7 cell lines. PIM-1/HDAC-IN-1 shows pre-G1 apoptosis and cell cycle arrest at G2/M phase.

HDAC-IN-50 is a potent and orally active FGFR and HDAC dual inhibitor with IC₅₀ values of 0.18, 1.2, 0.46, 1.4, 1.3, 1.6, 2.6, 13 nM for FGFR1, FGFR2, FGFR3, FGFR4, HDAC1, HDAC2, HDAC6, HDAC8, respectively. HDAC-IN-50 induces Apoptosis and cell cycle arrest at G0/G1 phase. HDAC-IN-50 decreases the expression of pFGFR1, pERK, pSTAT3. HDAC-IN-50 shows anti-tumor activity.

NHNB is a selective HDAC8 inhibitor (IC₅₀ = 66.0 μM) and Peptidoglycan N-acetylglucosamine (GlcNAc) deacetylases (PGNGdacs) inhibitor. NHNB shows antibacterial and bactericidal activity against B. anthracis and B. cereus. NHNB can be used for the research of acute myeloid leukemia, Bacillus anthracis infection, and Bacillus cereus infection.

Tubulin/HDAC-IN-1 is a dual tubulin and HDAC-IN-1 inhibitor through CH/π interaction with tubulin and hydrogen bond interaction with HDAC8. Tubulin/HDAC-IN-1 inhibits tubulin polymerization and selectively inhibits HDAC8 (IC₅₀: 150 nM). Tubulin/HDAC-IN-1 has cytotoxicity against various human cancer cells, also arrests cell cycle in the G2/M phase and induces cell apoptosis. Tubulin/HDAC-IN-1 can be used in the research of hematologic and solid tumors such as neuroblastoma, leukemia.

ZG-126 is an agonist for vitamin D receptor (VDR) and an inhibitor for histone deacetylase (HDAC) (IC₅₀=0.63-67.6 μM). ZG-126 exhibits cytotoxicity in cancer cells MDA-MB-231 and 4T1. ZG-126 exhibits antitumor and anti-metastatic efficacy against melanoma and triple-negative breast cancer (TNBC) in mouse models. ZG-126 also exhibits anti-inflammatory activity, through the reduction of macrophage infiltration and immunosuppressive M2-polarization.

SAHA-OH is a selective HDAC6 inhibitor (IC₅₀=23 nM), shows a 10- to 47-fold selectivity for HDAC6 compared to HDAC 1, 2, 3, and 8. SAHA-OH shows anti-inflammatory activity, and attenuates macrophage apoptosis.

HDAC-IN-30 is a novel multi-target HDAC inhibitor, including HDAC1 (IC₅₀=13.4 nM),HDAC2 (IC₅₀=28.0 nM), HDAC3 (IC₅₀=9.18 nM), HDAC6 (IC₅₀=42.7 nM), HDAC8 (IC₅₀=131 nM). HDAC-IN-30 exhibits potent antitumor efficacy.

Tubulin/HDAC-IN-3 (compound 12a) is a potent tubulin/HDAC dual inhibitor. Tubulin/HDAC-IN-3 effectively disrupts tubulin polymerization (IC₅₀: 5.4 μM). Tubulin/HDAC-IN-3 exhibits potent HDAC1/8 inhibitory activities, with IC₅₀ values of 0.155 and 0.177 μM, respectively. Tubulin/HDAC-IN-3 works through blocking cellular cycle, inducing apoptosis and inhibiting colony formation.

JN210 is a dual inhibitor of DCN1 and HDAC, with an IC₅₀ of 94.26 nM against human DCN1. JN210 disrupts the UBE2M-DCN1 protein-protein interaction, blocks the neddylation modification of cullin-RING ligases, inhibits HDAC activity and induces histone hyperacetylation. JN210 impairs DNA damage repair function, induces cell apoptosis, exerts cytotoxicity and inhibits tumor growth. JN210 can be used for the research of non-small cell lung cancer.

HDAC6-IN-43 (compound 26) is a potent HDAC inhibitor. HDAC6-IN-43 effectively inhibits several HDACs, notably HDAC1, HDAC2, and HDAC6 (IC₅₀ < 150 nM), displaying a particularly high sensitivity towards HDAC6 (IC₅₀ = 11 nM). HDAC6-IN-43 can be used for the research of autosomal dominant polycystic kidney disease (ADPKD).

HDAC-IN-93 is a HDAC inhibitor with promising total pan-HDAC inhibitory activity. HDAC-IN-93 demonstrates significant broad-spectrum antiproliferative activity across various cancer cell lines. HDAC-IN-93 induces cell apoptosis along with necrosis. HDAC-IN-93 can be used for the studies of prostate cancer and breast cancer.

HDAC-IN-84 (compound 4d) is a potent HDAC inhibitor, with IC₅₀ values of 0.0045, 0.015, 0.013, 0.038, 5.8 and 26 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8 and HDAC11, respectively. HDAC-IN-84 effectively inhibits the proliferation of leukemia cells without causing toxicity.

Quisinostat (JNJ-26481585) hydrochloride is a potent and orally active pan-HDAC inhibitor (HDACi), with IC₅₀ values ranging from 0.11 nM to 0.64 nM for HDAC1, HDAC2, HDAC4, HDAC10 and HDAC11. Quisinostat hydrochloride has a broad spectrum antitumoral activity. Quisinostat hydrochloride can induce autophagy in neuroblastoma cells.

HDAC-IN-47 is an orally active inhibitor of histone deacetylase (HDAC), with IC₅₀s of 19.75 nM (HDAC1), 5.63 nM (HDAC2), 40.27 nM (HDAC3), 57.8 nM (HDAC2), 302.73 nM (HDAC8), respectively. HDAC-IN-47 inhibits autophagy and induces apoptosis via the Bax/Bcl-2 and caspase-3 pathways. HDAC-IN-47 arrests cell cycle at G2/M phase, and shows anti-tumor efficacy in vivo.