HDAC6 Inhibitor

HDAC-IN-45 (Compound 14) is a small molecule HDAC inhibitor and has anticancer activity, also can forms a hydrogen bond with residue Y303. HDAC-IN-45 (Compound 14) has substantial inhibitory effects towards HDAC1, 2 and 3 isoforms with IC₅₀ values of 0.108, 0.585 and 0.563 μM respectively.

ROCK/HDAC-IN-1 (Compound 10h) is an orally active ROCK/HDAC inhibitor. ROCK/HDAC-IN-1 inhibits ROCK1/2 (IC₅₀: 254.9 nM, 58.18 nM) and HDAC1/2/3/6/8 (IC₅₀: 9.09, 8.03, 6.26, 0.41, 7.69 nM). ROCK/HDAC-IN-1 stimulates the activation of DAMPs, specifically Calreticulin (CRT) exposure and HMGB1 release, indicating that it is a potential ICD inducer.. ROCK/HDAC-IN-1 has antiproliferative activity against breast cancer cells (IC₅₀: 0.37 μM for MDA-MB-231 cell), and inhibits tumor growth and activates T cells without apparent toxicity.

HDAC6-IN-52 (EX.1) is a potent inhibitor of HDAC6, with the inhibitory rate of 100% at 10 μM. HDAC6-IN-52 plays an important role in central nervous system diseases including neurodegenerative diseases such as Alzheimer’s disease andprogressive supranuclear palsy.

HDAC-IN-36 (compound 23 g) is an orally active and potent HDAC (histone deacetylase) inhibitor, with an IC₅₀ of 11.68 nM (HDAC6). HDAC-IN-36 promotes apoptosis, autophagy and suppresses migration. HDAC-IN-36 shows anti-tumor and anti-metastatic activity, and can be used for breast cancer research.

HDAC6-IN-54 (Compound 9m) is a highly selective HDAC6 (histone deacetylase 6) inhibitor with an IC₅₀ value of 0.021 μM. HDAC6-IN-54 blocks the activation of the NLRP3 inflammasome, which alleviates symptoms of NLRP3 inflammasome-related diseases such as acute peritonitis, inflammatory bowel disease, and psoriasis.

Trichostatin C is an inhibitor for histone deacetylase (HDAC), induces apoptosis and arrests cell cycle at G2/M phase, and exhibits anticancer activity against lung cancer and urothelial bladder cancer. Trichostatin C induces differentation of Friend leukemic cells. Trichostatin C exhibits antifungal activity.

HDAC6-IN-15 is a selective histone deacetylase 6 (HDAC6) inhibitor. HDAC6-IN-15 has potent inhibitory activity for HDAC6 with IC₅₀ value of 38.2 nM. HDAC6-IN-15 can be used for the research of cancer and neurodegenerative diseases.

VEGFR2/HDAC-IN-1 is a dual selective enzymatic inhibitor of VEGFR2 kinase and HDAC6 with oral activity. VEGFR2/HDAC-IN-1 has an IC₅₀ of 19.19 nM for VEGFR2 and 0.165 μM for HDAC6. VEGFR2/HDAC-IN-1 increases α-tubulin acetylation, exerts antiproliferative effects, inhibits tumor growth, and exhibits antiangiogenic activity. VEGFR2/HDAC-IN-1 can be used for the research of colorectal carcinoma and hepatocellular carcinoma.

NMDAR/HDAC-IN-1 (Compound 9d) is a dual NMDAR and HDAC inhibitor with a K_i of 0.59 μM for NMDAR and IC₅₀ values of 2.67, 8.00, 2.21, 0.18 and 0.62 μM for HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8, respectively. NMDAR/HDAC-IN-1 efficiently penetrates the blood brain barrier.

DS-103 is an inhibitor for HDAC that inhibits HDAC1, HDAC2, HDAC3, HDAC6 and HDAC8 with IC₅₀s of 0.029, 0.123, 0.022, 0.367 and 9.26 μM, respectively. DS-103 inhibits Plasmodium falciparum 3D7 with IC₅₀ of 5.08 μM. DS-103 exhibits cytotoxicity in cells A2780 and Cal27 with IC₅₀ of 1.48 μM and 1.47 μM, reverses Cisplatin (HY-17394) resistance in A2780 and Cal27 with IC₅₀ of 4.62 μM and 2.23 μM. DS-103 exhibits synergistic effect with Cisplatin (HY-17394), enhances Cisplatin-induced apoptosis.

MPT0G413 (Compound 6) is a potent, selective, orally active and brain-penetrant HDAC6 inhibitor with an IC₅₀ of 3.92 nM. MPT0G413 decreases not only the level of phosphorylation of tau proteins but also the aggregation of tau proteins. MPT0G413 can ameliorate the impaired learning and memory. MPT0G413 can be used for the research of neurological disease, such as Alzheimer's disease.

HDAC1/6-IN-2 (I-c4) is the inhibitor of HDAC1 and HDAC6, with the IC₅₀s of 3.1 nM and 2.95 nM, respectively. HDAC1/6-IN-2 has antitumor activity.

TNI-97 is a selective and orally active HDAC6 inhibitor, with an IC₅₀ of 0.2 nM. TNI-97 potently inhibited TNBC cell MDA-MB-453 growth and clonogenicity. TNI-97 induces PANoptosis including apoptosis, necroptosis and pyroptosis in MDA-MB-453 cells. TNI-97 shows antitumor activity in the mice carrying the MDA-MB-453 xenograft or carrying murine-derived TNBC cell allografts. TNI-97 can be used for the study of triple-negative breast cancer.

HDAC6-IN-84 is a potent and selective HDAC6 inhibitor with an IC₅₀ of 25.56 nM and shows 478-fold selectivity over HDAC1. HDAC6-IN-84 increases α-tubulin acetylation and upregulates BDNF (exons I and IV) and other neurogenesis-related genes. HDAC6-IN-84 can be used for the study of Alzheimer’s disease (AD) and other neurodegenerative diseases.

PTG-0861 is a selective histone deacetylase 6 (HDAC6) inhibitor with the IC₅₀ value of 5.92 nM. PTG-0861 induces apoptosis and can be used in the study of acute myeloid leukemia, multiple myeloma and other hematological cancers.

HDAC10-IN-2 (compound 10c) is a potent and highly selective HDAC10 inhibitor, with an IC₅₀ of 20 nM. HDAC10-IN-2 modulates autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.

HIT211504993 is a selective histone deacetylase 6 (HDAC6) inhibitor with an IC₅₀ of 0.070 μM. HIT211504993 suppresses cancer cell proliferation, cause G1 phase cell cycle arrest and induces apoptosis. HIT211504993 inhibits Myc-driven tumorigenesis via nucleocytoplasmic acetylation, p53 modulation, and Wnt/β-catenin signaling modulation. HIT211504993 inhibits tumor growth in a colon cancer xenograft mouse model. HIT211504993 can be used for the research of colon cancer.

Syk/HDAC6-IN-1 is a dual SYK/HDAC6 selective inhibitor with IC₅₀ values of 0.19 nM (SYK) and 0.66 nM (HDAC6). Syk/HDAC6-IN-1 downregulates p-SYK to block downstream AKT/FOXO1 signaling, elevates acetylated histone H3 and α-tubulin via HDAC suppression, represses SREBF1 -mediated lipid biosynthetic pathways, triggers G0/G1 cell cycle arrest and robust mitochondrial-dependent caspase-3-mediated apoptosis in leukemia cells. Syk/HDAC6-IN-1 can be used for the research of FLT3-mutant acute myeloid leukemia.

ZSNI-21 is a ADAM17/HDAC2 inhibitor with ADAM17 IC₅₀ 0.939 μM and HDAC2 IC₅₀ 0.844 μM. ZSNI-21 regulates the expression of apoptosis-related proteins (Bax, Bcl-2) and Cyclin D1, and induces apoptosis.. ZSNI-21 can be used for the research of hepatocellular carcinoma, breast cancer, and non-small cell lung cancer.

NR160 is a selective HDAC6 inhibitor with an IC₅₀ value of 30 nM. NR160 shows low cytotoxicity against leukemia cell line. NR160 augments the apoptosis induction of Bortezomib (HY-10227) (proteasome inhibitor), Epirubicin (HY-13624) and Daunorubicin (HY-13062A) significantly.