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.

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

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.

HDAC4 CHDI Degrader 11 is a potent, selective degrader of HDAC4 (PROTAC) with DC_50 values of 4 nM and 6 nM in Jurkat E6-1 and Jurkat cells, respectively. This compound integrates the class IIa HDAC inhibitor trifluoromethyloxadiazole with a ligand for the Von Hippel-Lindau (VHL) protein through a linker. Demonstrating significant efficacy, HDAC4 CHDI Degrader 11 achieves a DC_50 value of 1 nM in a mouse cell model of Huntington's disease. For enhanced degradation in neuroblastoma cell lines, it can be administered alongside the P-glycoprotein inhibitor, Elacridar.

HDAC/JAK/BRD4-IN-1 (compound 25ap) is a potent triple inhibitor targeting HDAC, JAK, and BRD4. This compound not only inhibits cell proliferation but also induces apoptosis in MDA-MB-231 cells and demonstrates in vivo anticancer efficacy [1].

HDAC8-IN-4 is a selective HDAC8 inhibitor with IC50 values of 0.15 μM for HDAC8 and 12 μM for HDAC3 [1].

HDAC6-IN-4 (C10) is an orally active, highly selective HDAC6 inhibitor with an IC50 of 23 nM. It induces apoptosis and demonstrates potent anti-tumor effects while exhibiting non-significant toxicity.

G4/HDAC-IN-1, a dual-targeting compound for G4 and HDAC, shows inhibition of intracellular HDAC activity, with an IC50 value of 1.1 μM, and promotes G4 formation. It effectively inhibits proliferation and tumor growth in a TNBC xenograft model, presenting potential for cancer research applications.

HDAC3-IN-4 is a selective and orally active inhibitor of HDAC3, boasting an IC50 of 89 nM. It induces the degradation of PD-L1 by modulating cathepsin B (CTSB) in lysosomes, with a DC50 of 5.7 μM. Compared to HDAC1, HDAC6, HDAC7, and HDAC8, HDAC3-IN-4 demonstrates superior selectivity for HDAC3.

HDAC1-IN-4 is a potent inhibitor of Plasmodium falciparum HDAC1 (PfHDAC1) with low cytotoxicity and antimalarial effects (IC50<5 nM).

HDAC4-IN-1 (compound 1a), a class IIa HDACI inhibitor with an IC 50 of 0.077 μM, exhibits anticancer activity by enhancing Caspase-induced apoptosis. It is also utilized in cancer drug combination research [1].

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.

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

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.

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].

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

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.

JAK HDAC-IN-2, a potent 2-amino-4-phenylaminopyrimidine dual-target inhibitor, effectively suppresses JAK1 2 and HDAC3 6 at nanomolar concentrations. This compound exhibits proapoptotic properties, inhibits histone deacetylation, and impedes STAT3 phosphorylation, demonstrating notable antiproliferative activity against various hematological malignancies and solid tumors [1].

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)