hdacin4

HDAC-IN-4, a selective HDAC6 and HDAC10 inhibitor (pIC50s: 7.2 and 6.8 in the BRET assay), exhibits antitumoral activity.

c-Met/HDAC-IN-4, a dual inhibitor of c-Met/HDAC, exhibits an IC 50 value of 28.92 nM for c-Met. This compound effectively induces G 0 /G 1 phase cell cycle arrest and apoptosis in MDA-MB-231 breast cancer cells. Additionally, c-Met/HDAC-IN-4 suppresses both the proliferation and invasion of breast cancer cell lines.

CDK/HDAC-IN-4 is a highly selective dual inhibitor of cyclin-dependent kinase (CDK) and histone deacetylase (HDAC), with IC50 values of 88.4 nM and 168.9 nM, respectively. This compound exhibits antiproliferative effects in both hematologic and solid tumor cells. Additionally, CDK/HDAC-IN-4 induces apoptosis and S-phase cell cycle arrest in MV-4-11 cells. It has also demonstrated significant antitumor efficacy in an MV-4-11 xenograft model.

JAK/HDAC-IN-4 (compound 11 i) is a dual inhibitor targeting both JAK2 and HDAC6, with IC50 values of 0.49 nM and 12 nM respectively. It inhibits cell proliferation and the production of nitric oxide. In a mouse model induced by Imiquimod, JAK/HDAC-IN-4 ameliorates psoriasiform skin lesions with low toxicity.

PI3K/HDAC-IN-4 (Compound 31f) is a dual inhibitor targeting PI3K and HDAC, with an IC50 of 0.2μM. It demonstrates high selectivity for HDAC1-3, with IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively. As a potent pan-PI3K inhibitor, PI3K/HDAC-IN-4 has IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. This compound effectively induces apoptosis in tumor cells by concurrently inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. It shows significant antiproliferative activity across various tumor cell lines, such as 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 is applicable in the study of lymphoma and leukemia.

Tubulin/HDAC-IN-4 (compound 9n) is a dual inhibitor targeting microtubules (Tubulin) and HDAC, exhibiting IC50 values of 0.73, 0.43, 0.62, and 2.34 µM for HDAC1, HDAC2, HDAC6, and HDAC7, respectively. It disrupts microtubule assembly by binding to the colchicine site and induces apoptosis and G2/M cell cycle arrest. Additionally, Tubulin/HDAC-IN-4 significantly increases intracellular ROS levels and demonstrates both anti-angiogenic and anticancer properties.

HDAC-IN-40 is a potent alkoxyamide-based HDAC inhibitor with a Ki of 60 nM for HDAC2 and 30 nM for HDAC6, exhibiting antitumor effects.

HDAC-IN-42 (compound 14f) is a highly potent and selective inhibitor of histone deacetylase (HDAC) enzymes, with IC50 values of 0.19 μM for HDAC1 and 4.98 μM for HDAC6. It exhibits significant anticancer properties, inhibiting cell proliferation, inducing apoptosis, and causing cell cycle arrest specifically at the G2/M phase [1].

HDAC-IN-47 is an orally active histone deacetylase (HDAC) inhibitor, with IC50 values of 19.75 nM, 57.8 nM, 40.27 nM, 5.63 nM, and 302.73 nM for HDAC1, HDAC2, HDAC3, HDAC6, and HDAC8, respectively. HDAC-IN-47 can block the cell cycle in the G2/M phase, inhibit autophagy, induce apoptosis via the Bax/Bcl-2 and caspase-3 pathways, and exhibits anti-cancer activity in vivo.

HDAC-IN-46 (compound 12c) is a potent inhibitor of HDAC, targeting HDAC1 (IC50: 0.21 μM) and HDAC6 (IC50: 0.021 μM). It upregulates p-p38, downregulates Bcl-xL and cyclin D1 in MDA-MB-231 cells, blocks the cell cycle in the G2 phase, and induces apoptosis, making it useful for triple negative breast cancer (TNBC) studies.

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

HDAC-IN-41 (Compound 7c) is an orally active, selective class I HDAC inhibitor targeting HDAC1 (IC50: 0.62 μM), HDAC2 (IC50: 1.46 μM), and HDAC3 (IC50: 0.62 μM). HDAC-IN-41 also exhibits NO-releasing activity.

HDAC-IN -45, a small molecule HDAC inhibitor, was able to form hydrogen bonds with Y303 residues and exhibited anticancer effects. HDAC-IN-45 significantly inhibited HDAC1, HDAC2 and HDAC3 subtypes with their IC50 values of 0.108, 0.585 and 0.563 μM, respectively.

HDAC-IN-44 is an HDAC inhibitor (IC50: 61.2 nM) with strong anti-cancer effects.

HDAC-IN-49 is a potent, non-selective inhibitor of HDAC (HDAC), demonstrating IC50 values of 13 nM for HDAC1, 14 nM for HDAC2, 21 nM for HDAC3, 1880 nM for HDAC4, and 10 nM for HDAC6. This compound exhibits significant antileukemic activity while maintaining low cytotoxicity towards healthy cells.

HDAC-IN-4-d4 is a deuterated compound of HDAC-IN-4.