HDAC6 Inhibitor

HDAC6-IN-85 is a selective HDAC6 inhibitor, with pIC₅₀ values of 5.4, 5.5, 5.9, and 4.8 against rHDAC1, rHDAC3, rHDAC6, and rHDAC8, respectively. HDAC6-IN-85 can be used in the research of cervical cancer, lung cancer, and colon cancer.

HDAC6-IN-10 is a highly selective HDAC6 inhibitor with the IC₅₀ of 0.73 nM. HDAC6-IN-10 has 144~10941-fold selectivity over other HDAC isoforms. HDAC6-IN-10 shows anti-proliferative activities against multiple myeloma cells.

HDAC-IN-99 is a histone deacetylase (HDAC) inhibitor with an IC₅₀ of 37.73 nM, and it exhibits potent inhibitory activity against HDAC1 (IC₅₀ = 48.09 nM), HDAC2 (IC₅₀ = 300.28 nM) and HDAC6 (IC₅₀ = 9.16 nM). HDAC-IN-99 exerts broad-spectrum antiproliferative activity in various cancer cell lines. HDAC-IN-99 induces S-phase cell cycle arrest and apoptosis in colon cancer cells, increases the acetylation levels of histone H3, histone H4 and α-tubulin, and upregulates the expression of p21 as well as the cleavage of caspase-3. HDAC-IN-99 displays antitumor activity in colon cancer xenograft models. HDAC-IN-99 can be used for the research of colon cancer.

HDAC-IN-35 (Compound 14) is a potent, selective HDAC and VEGFR-2 inhibitor, with IC₅₀ values of 0.166 and 13.2 µM for HDAC6 and VEGFR-2, respectively.

PDE5/HDAC-IN-1 (Compound 26) is a potent phosphodiesterase 5 (PDE5) and HDAC inhibitor with IC₅₀ values of 46.3 nM and 14.5 nM, respectively. PDE5/HDAC-IN-1 induces cell apoptosis and shows anticancer activities.

HDAC6-IN-73 is a highly potent and selective HDAC6 inhibitor with an IC₅₀ of 0.007 μM ± 0.001, ~1771-fold selectivity over HDAC1, ~131-fold selectivity over HDAC8, and antiproliferative activity in hematological cancer cell lines.HDAC6-IN-73 can be used for the research of hematological malignancies.

HDAC-IN-38 (compound 13) is a potent HDAC inhibitor. HDAC-IN-38 shows similar micro-molar inhibitory activity toward HDAC1, 2, 3, 5, 6, and 8. HDAC-IN-38 increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy. HDAC-IN-38 also increases the level of histone acetylation (H3K14 or H4K5).

HDAC6-IN-35 (compound C4 (ZINC000077541942)) is a potent and BBB-penetrated HDAC6 inhibitor with the IC₅₀ of 4.7 μM. HDAC6-IN-35 shows cell toxicity against MDA-MB-231 with EC₅₀ of 40.6 μM.

ALK/HDAC-IN-2 (Compound 19b) is an ALK/HDAC inhibitor with IC₅₀ values for ALK WT and total HDACs of 8 nM and 1.18 μM, respectively. ALK/HDAC-IN-2 exhibits inhibitory activity against ALK mutants G1202R, F1174L, and L1196M, with IC₅₀ values of 2.74, 9.23, and 34.28 nM, respectively. ALK/HDAC-IN-2 shows potent and selective inhibition against HDAC1 (IC₅₀ = 0.24 μM), while its inhibitory activity against HDAC7, HDAC6, and HDAC11 is weak (IC₅₀ > 10 μM). ALK/HDAC-IN-2 has broad-spectrum anti-proliferative activity against various cancer cells, inducing cell cycle arrest and apoptosis. ALK/HDAC-IN-2 can be used for the study of neuroblastoma.

HDAC-IN-43 is a potent HDAC 1/3/6 inhibitor with IC₅₀ values of 82, 45, and 24 nM, respectively. HDAC-IN-43 is a weak PI3K/mTOR inhibitors with IC₅₀ values of 3.6 and 3.7 μM, respectively. HDAC-IN-43 shows broad anti-proliferative activity .

HDSI-18 is an orally active HDAC6 selective inhibitor (IC₅₀: 1.6 nM). HDSI-18 is cytotoxic to K562, MV4-11, MOLM-13, THP-1, and Jurkat cells (IC₅₀: 0.48, 0.58, 0.91, 1.79, and 4.31 μM, respectively). HDSI-18 activates Caspase-3, induces mitochondrial depolarization and apoptosis, and has antitumor activity.

HDAC6-IN-27 (compound 8C) is a HDAC inhibitor with IC₅₀ vales of 15.9 nM 136.5 nM and 6180.2 nM for HDAC6, HDAC8 and HDAC1, respectively. HDAC6-IN-27 shows potent antiparasitic effects.

MC2590 is a potent pyridine-containing histone deacetylase (HDAC) inhibitor. MC2590 is a inhibitor of HDAC1-3, -6, -8, and -10 (class I/IIb-selective inhibitor) with IC₅₀s of 0.015 μM-0.156 μM. MC2590 also inhibits HDAC isoforms HDAC4, HDAC5, HDAC7, HDAC9, HDAC11 with IC₅₀s of 1.35 μM-3.98 μM. MC2625 induces G2/M cell cycle arrest and modulates pro- and anti-apoptotic microRNAs towards apoptosis induction.

HDAC-IN-94 is a potent, selective HDAC6 inhibitor (IC₅₀ = 4.5 nM). HDAC-IN-94 shows >1000-fold selectivity over HDAC8 and shows minimal activity against other isoforms (HDAC1-3/10). HDAC-IN-94 induces α-tubulin hyperacetylation, apoptosis, and G2/M cell cycle arrest, exhibiting potent anti-tumor efficacy with low cytotoxicity. HDAC-IN-94 can be used for neuroblastoma and glioblastoma research.

DNMT/HDAC-IN-2 (Compound Y7) is a DNMT and HDAC inhibitor with IC₅₀ values for DNMT1, HDAC1, and HDAC6 of 365, 0.2, and 8.91 nM respectively. DNMT/HDAC-IN-2 inhibits the proliferation of breast cancer cells. DNMT/HDAC-IN-2 significantly reduces tumor growth in xenografts and transgenic breast cancer mouse models. DNMT/HDAC-IN-2 can be used for the study of breast cancer.

HDAC1-IN-11 (Compound 6) is a HDAC1 inhibitor with an IC₅₀ of 106.6  nM. HDAC1-IN-11 inhibits the expression of Sp1 and RAD51, thereby inducing Caspase-dependent apoptosis. HDAC1-IN-11 has antitumor activity and sensitizes Etoposide (HY-13629) and Gemcitabine (HY-17026), promoting synergistic death of NSCLC cells through the inhibition of homologous recombination and non-homologous end joining (NHEJ) pathways involved in DNA DSB repair. HDAC1-IN-11 can be used for chemotherapy of cancers like NSCLC research.

PPM-18 (NSC 73233) is a Vitamin K (HY-B2172) analog. PPM-18 prevents LPS-induced IκBα degradation, thereby inhibiting NF-κB activation and nuclear translocation of NF-κB. PPM-18 inhibits LPS-induced nitrite production and iNOS expression. PPM-18 inhibits HDAC6. PPM-18 induces ROS accumulation, activates AMPK, inhibits the mTORC1 and PI3K/AKT pathways, initiates Autophagy, and induces Apoptosis. PPM-18 suppresses seizures in zebrafish and mouse epilepsy models. PPM-18 prevents LPS-induced lethal toxicity and delayed hypotension. PPM-18 exhibits anticancer activity against leukemia and bladder cancer. PPM-18 can be used in research related to septic shock, bladder cancer and atherosclerosis.

CDK/HDAC-IN-2 is a potent HDAC/CDK dual inhibitor with IC₅₀ of 6.4, 0.25, 45, >1000, 8.63, 0.30, >1000 nM for HDAC1, HDAC2, HDAC3, HDAC6,8, CDK1, CDK2, CDK4,6,7, respectively. CDK/HDAC-IN-2 shows excellent antiproliferative activities. CDK/HDAC-IN-2 induces apoptosis and cell cycle arrest at G2/M phase. CDK/HDAC-IN-2 shows potent antitumor efficacy.

HDAC6 ligand-7 (Compound 16a) is a positron emission tomography (PET) tracer for the deacetylase 6 (HDAC6) enzyme with a K_d value of 1.66 nM. HDAC6 ligand-7 exhibits excellent HDAC6 inhibitory activity, with IC₅₀ values of 2.7 and 3.7 nM for hHDAC6 and mHDAC6, respectively, and has high selectivity for HDAC1/4/7/8. HDAC6 ligand-7 after being radioactively labeled with fluorine-18, [¹⁸F]HDAC6 ligand-7 shows varying degrees of radioactive uptake in PET, which can reflect the specific binding to HDAC6. HDAC6 ligand-7 can be used for the study of HDAC6 imaging.

HDAC6-IN-11 (Compound 9) is a selective HDAC6 inhibitor with the IC₅₀ value of 20.7 nM. HDAC6-IN-11 has more than 300-fold selectivity over HDAC other isoforms. HDAC6-IN-11 shows anti-proliferative activities against cancer cells.