hdac-in-4

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.

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

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 HSP90-IN-4 significantly inhibited HDAC and HSP90 activity, with compound 20 (HDACIC50= 194 nM; HSP90αIC50= 153 nM) and compound 26 ((HDACIC50= 360 nM; HSP90αIC50= 77 nM) having the strongest HDAC and HSP90α inhibition. effect. Both compounds induced HSP90 expression and down-regulated HSP90 client proteins, which play an important role in the regulation of cancer cell survival and invasion.

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.

CHDI-390576 is a CNS-permeable, selective and potent dibenzoyl isohydroxamic acid class IIa histone deacetylase (HDAC) inhibitor that inhibits class IIa HDAC 4, HDAC 5, HDAC 7, HDAC 9, and can be used in cancer research.

FLT3 HDAC-IN-1 is a dual inhibitor targeting FLT3 and HDAC, with IC50 values of 30.4 nM for FLT3 and 52.4, 14.7 nM for HDAC1 3, respectively. It induces apoptosis in MV-4-11 cells and exhibits antiproliferative effects against BaF3 cells transformed by FLT3 mutations. FLT3 HDAC-IN-1 is useful for research on refractory solid tumors and hematological malignancies.

HDAC-IN-79 (compound 4) is an orally active dual inhibitor of xanthine oxidase and HDAC, exhibiting potent anti-hyperuricemia and antitumor activities in vivo (Xanthine oxidase: IC50=6.6 nM; HDAC1: IC50=134 nM; HDAC2: IC50=284 nM; HDAC3: IC50=173 nM; HDAC6: IC50=1.32 nM). Among leukemia cells, it is most effective in inhibiting the growth of HL60 cells (IC50=0.706 μM) and induces both apoptosis and autophagy. HDAC-IN-79 also modulates the expression levels of biomarkers associated with intracellular HDAC inhibition.

4-Chloro-6,7-bis(2-methoxyethoxy)quinazoline is a building block and synthetic intermediate.1,2,3,4,5It has been used as a precursor in the synthesis of receptor tyrosine kinase (RTK) inhibitors, dual RTK and histone deacetylase (HDAC) inhibitors, and anticancer compounds.1,2,3It is also a synthetic intermediate in the synthesis of EGFR inhibitors, including erlotinib , with antiproliferative activity.4,5

TW9 is a dual inhibitor of bromodomain 2 (BD2) in bromodomain-containing protein 4 (BRD4) and histone deacetylase 1 (HDAC1; IC50s = 0.074 and 0.29 μM, respectively).1It is selective for BD2 over BD1 in BRD4 (IC50= 0.72 μM) and for HDAC1 over HDAC2 (IC50= 2.5 μM). TW9 (50 nM) induces apoptosis in, and inhibits proliferation of, MIA PaCa-2 pancreatic cancer cells. It induces cell cycle arrest at the G1phase in HPAC pancreatic cancer cells when used at a concentration of 2 μM. TW9 acts synergistically with gemcitabine to reduce the viability of HPAC cells. 1.Zhang, X., Zegar, T., Weiser, T., et al.Characterization of a dual BET HDAC inhibitor for treatment of pancreatic ductal adenocarcinomaInt. J. Cancer147(10)2847-2861(2020)

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

Theophylline (1,3-Dimethylxanthine) sodium glycinate is a potent phosphodiesterase (PDE) inhibitor that targets PDE3 to relax airway smooth muscle and is used in asthma and chronic obstructive pulmonary disease (COPD) research. It also functions as an adenosine receptor antagonist, histone deacetylase (HDAC) activator, and exhibits anti-inflammatory activity by increasing IL-10 levels and inhibiting NF-κB nuclear import, while inducing apoptosis [1] [2] [3] [4] [5].

CDK HDAC-IN-1 exhibits potent inhibitory activity towards CDK2 4 6 and HDAC6, with IC50 values of 60.9 ± 2.9 nM, 276 ± 22.3 nM, 27.2 ± 4.2 nM, and 128.6 ± 0.4 nM, respectively.

Quisinostat dihydrochloride (JNJ26854165(Quisinostat) 2HCl) is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM in a cell-free assay, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7. Phase 2.