HDAC2 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.

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.

Largazole ((+)-Largazole) is an orally active, blood-brain barrier-permeable class I histone deacetylase (HDAC) inhibitor with in vivo anticancer activity and osteogenic efficacy. As a prodrug, Largazole hydrolyzes to Largazole thiol (HY-170890), which has a K_i value of 0.07 nM against human HDAC2. Largazole regulates the cell cycle, induces apoptosis, upregulates tumor suppressors and osteoblast differentiation markers, inhibits osteoclast formation, and upregulates neuroprotection-related genes. Largazole can be used in the research of various cancers including colorectal cancer, as well as neurodegenerative diseases.

HDAC ligand-5 is a template for the non-selective HDAC inhibitor Vorinostat (HY-10221). HDAC ligand-5 can serve as a ligand for target protein (Ligands for Target Protein for PROTAC) for the development of PROTAC HDAC degraders with antitumor activity. HDAC ligand-5 can be used for the synthesis of FF2049 (HY-168863).

HDAC6-IN-44 (compound H10) is a selective HDAC6 inhibitor with an IC₅₀ value of 8.97 nM. HDAC6-IN-44 can inhibit the idiopathic pulmonary fibrosis (IPF) phenotype and exhibits antifibrotic activity. Additionally, HDAC6-IN-44 reduces fibrogenesis in a bleomycin-induced pulmonary fibrosis mouse model and demonstrates good metabolic stability. HDAC6-IN-44 holds promise for research in the field of idiopathic pulmonary fibrosis.

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.

HDAC6-IN-14 is a highly selective HDAC6 (HDAC) inhibitor with an IC₅₀ of 42 nM. HDAC6-IN-14 displays >100-fold selectivity over HDAC1/HDAC2/HDAC3/HDAC4.

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.

HDAC-IN-54 is a HDAC inhibitor with an IC₅₀ of 25 nM against human HDAC1, 66 nM against HDAC2, 6.5 nM against HDAC3, and 281 nM against HDAC6. HDAC-IN-54 induces acetylation of α-tubulin and histone H3. HDAC-IN-54 acts synergistically with cisplatin to induce cancer cell apoptosis. HDAC-IN-54 can be used in research related to head and neck cancer, ovarian cancer, and tongue squamous cell carcinoma.

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.

HDAC-IN-49 is a potent unselective HDAC (HDAC) inhibitor with IC₅₀s of 13 nM, 14 nM, 21 nM, 1880 nM, and 10 nM for HDAC1, HDAC2, HDAC3, HDAC4, and HDAC6. HDAC-IN-49 demonstrates prominent antileukemic activity with low cytotoxic activity toward healthy cells.

HDAC2-IN-3 is a selective, orally active, blood-brain barrier permeable HDAC2 inhibitor with an IC₅₀ of 14 nM. HDAC2-IN-3 upregulates histone acetylation levels in cells and in vivo, and enhances long-term potentiation (LTP) in the hippocampus. HDAC2-IN-3 can be used for the research of Alzheimer's disease.

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).

HDAC6-IN-70 (Compound 9q) is a selective HDAC6 inhibitor with an IC₅₀ of 29 nM. HDAC6-IN-70 effectively inhibits tubulin polymerization and HDAC6. HDAC6-IN-70 causes Apoptosis. HDAC6-IN-70 shows anticancer effects on hematological malignancies and colorectal cancers.