HDAC6 Inhibitor

HDAC6-IN-64 (Compound 8) is a HDAC6 inhibitor with an IC₅₀ of 11.9  nM. HDAC6-IN-64 has poor cell permeability. HDAC6-IN-64 can be used for chemotherapy of cancers like NSCLC research.

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.

DNA-PK/HDAC6-IN-1 is a selcetive and orally active dual DNA-PK and HDAC6 inhibitor with IC₅₀ values of 84.2 and 64.8 nM. DNA-PK/HDAC6-IN-1 suppresses cancer cells proliferation, induces cancer cell cycle G2/M arrest, apoptosis, and decreases the mitochondrial membrane potential. DNA-PK/HDAC6-IN-1 induces DNA damage and elevates γ-H2AX levels. DNA-PK/HDAC6-IN-1 exhibits antitumor efficacy in AML animal mouse model. DNA-PK/HDAC6-IN-1 can be used for the research of acute myeloid leukemia.

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.

NS06 is a dual-target inhibitor of STAT3 and HDAC, with a K_d of 5.82 μM for human STAT3, an IC₅₀ of 129.1 nM for human HDAC1, an IC₅₀ of 451.2 nM for human HDAC3, and an IC₅₀ of 230.4 nM for human HDAC6. NS06 binds to STAT3 to inhibit its phosphorylation without altering the total STAT3 level; it inhibits the enzymatic activity of HDAC via coordination with Zn²⁺ at the catalytic center of HDAC1 and increases the acetylation level of histone H3. NS06 induces cell apoptosis, inhibits cancer cell migration and colony formation, and exhibits antiproliferative activity against solid tumor cells and 3D tumor spheroid models. NS06 is applicable to solid tumor-related research.

HDAC/CK2-IN-1 (compound 38) is a HDAC1 (IC₅₀ = 1.46 μM), HDAC6 (IC₅₀ = 0.66 μM), and CK2 (IC₅₀ = 3.67 μM) inhibitor. HDAC/CK2-IN-1 exhibits promising antproliferative activity against Jurkat, MCF-7, HCT-116, and HL-60 cell lines.

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.

HDAC-IN-34 (compound 27) is a potent HDAC inhibitor, with IC₅₀ values of 0.022 and 0.45 μM for HDAC1 and HDAC6, respectively. HDAC-IN-34 can bind to DNA and cause DNA damage. HDAC-IN-34 causes cells apoptosis through p53 signaling pathway. HDAC-IN-34 exhibits significant anti-proliferation effect against HCT-116 cells, with an IC₅₀ of 1.41 μM.

DNA-PK/HDAC6-IN-2 is an orally active and selective dual-target inhibitor of DNA-PK and HDAC6, with an IC₅₀ of 34.22 nM for DNA-PK and an IC₅₀ of 241.2 nM for HDAC6. DNA-PK/HDAC6-IN-2 upregulates Ac‑α‑tubulin, inhibits p‑DNA‑PK, and increases γ‑H2AX. DNA-PK/HDAC6-IN-2 exhibits antiproliferative activity against multiple solid tumor cell lines, induces apoptosis and cell cycle arrest, and inhibits migration and invasion. DNA-PK/HDAC6-IN-2 has in vivo antitumor efficacy in melanoma and breast cancer models and enhances the efficacy of Doxorubicin (HY-15142A). DNA-PK/HDAC6-IN-2 can be used for research on various cancers such as melanoma, breast cancer, and colorectal cancer.

HDAC6-IN-76 (Compound G25) is a selective HDAC6 inhibitor with an IC₅₀ of 12 nM. HDAC6-IN-76 induces Autophagy in a p53-dependent manner. HDAC6-IN-76 induces Apoptosis in a p53-dependent manner. HDAC6-IN-76 exhibits anticancer activity against hematologic malignancies, including acute myeloid leukemia.

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.

HDAC1-IN-5 is a potent HDAC1 inhibitor with IC₅₀ values of 15 nM and 20 nM for HDAC1 and HDAC6, respectively. HDAC1-IN-5 can enhance the acetylation of histone H3 and α-tubulin, as well as promote the activation of caspase 3 in cancer cells, thereby inducing apoptosis. HDAC1-IN-5 induces chromatin damage by binding with DNA. HDAC1-IN-5 has strong inhibitory activity against tumor growth in xenograft mice.

HDAC6-IN-60 (Compound 12) is an orally active and selective HDAC6 inhibitor. HDAC6-IN-60 exerts effects on tumor cell proliferation by inhibiting the enzymatic activity of HDAC6 and regulating pathways related to protein homeostasis. HDAC6-IN-60 is promising for research of HDAC6- related cancers.

HDAC6-IN-59 (Compound 38k) is a highly selective histone deacetylase 6 (HDAC6) inhibitor (IC₅₀=3.12 nM, with 352-fold selectivity over HDAC1). HDAC6-IN-59 is promising for research of esophageal 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.

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.

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.