HDAC3 Inhibitor

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.

cGAS/HDAC-IN-1 is an orally active dual cGAS/HDAC inhibitor that exhibits potent inhibitory activity against human and mouse cGAS (IC₅₀: 0.17 and 1.80 μM, respectively) and moderate activity against HDAC3 and HDAC6 (IC₅₀: 1.2 and 0.4 μM, respectively). cGAS/HDAC-IN-1 directly suppresses cGAS activity and increases its acetylation levels via HDAC3 inhibition. cGAS/HDAC-IN-1 is effective in murine models of inflammatory bowel disease and Aicardi-Goutières syndrome, and can be used in research on cGAS-dependent disorders.

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.

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.

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-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.

PI3K/HDAC-IN-4 (Compound 31f) is a PI3K/HDAC dual inhibitor (IC₅₀: 0.2μM). PI3K/HDAC-IN-4 shows high selectivity for HDAC1-3 (IC₅₀ values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively). PI3K/HDAC-IN-4 is a potent PIK3 inhibitor with IC₅₀ values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. PI3K/HDAC-IN-4 significantly induces tumor cell apoptosis by simultaneously inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. PI3K/HDAC-IN-4 exhibits potent antiproliferative activity in a variety of tumor cell lines (e.g., MV4-11, Jeko-1, HL60, and MCF-7, with IC₅₀ values of 0.2, 0.9, 0.8, and 1.5 μM, respectively). PI3K/HDAC-IN-4 can be used in the study of lymphoma and leukemia.

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.

HDAC1/3-IN-1 is a selective HDAC1/3 inhibitor, with IC₅₀ values of 256 nM and 340.3 nM against HDAC1 and HDAC3, respectively. HDAC1/3-IN-1 increases the SubG1 cell population and promotes apoptosis of glioma cells and glioblastoma stem cells. HDAC1/3-IN-1 can be used in studies related to glioblastoma.

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.

HDAC-IN-27 (Compound 11h) is a potent, orally active class I HDAC-selective inhibitor with IC₅₀ values ranging from 0.43 to 3.01 nM against HDAC1-3. HDAC-IN-27 exhibits both in vivo and in vitro antitumor activity. HDAC-IN-27 demonstrates significant anti-proliferative activity against acute myeloid leukemia (AML) cell lines by inducing apoptosis and histone acetylation (AcHH3 and AcHH4). HDAC-IN-27 can be used for research in acute myeloid leukemia (AML).

CM-444 is inhibitor for HDAC (IC₅₀ is 6 nM-0.6 μM) and DNA methyltransferases (DNMT, IC₅₀ is 1.8-2.3 μM). CM-444 is an inducer for the differentiation of acute myeloid leukemia cells. CM-444 exhibits anti-leukemic activity and improves the survival rate in mouse models.

EGFR/HDAC-IN-2 (Compound 38) is dual-functional inhibitor of EGFR and HDAC3 with IC₅₀s of 20.34 and 1.09 nM for CDK9 and HDAC3, respectively. EGFR/HDAC-IN-2 has superior anti-proliferative activity against cancer cells, inhibits cell migration and induces late-stage cell apoptosis. EGFR/HDAC-IN-2 significantly inhibits triple-negative breast cancer (TNBC) tumor growth in xenograft mouse models. EGFR/HDAC-IN-2 can be used for cancers like TNBC research.