HDAC3-IN-T326 is a potent and selective HDAC3 inhibitor that acts by increasing NF-κB acetylation and activating HIV gene expression in latent HIV-infected cells.
HDAC8-IN-3 (compound P19) is a highly potent inhibitor of HDAC8, displaying an IC50 value of 9.3 μM and producing thermal stabilization. Moreover, HDAC8-IN-3 exhibits cytotoxicity and induces apoptosis specifically in leukemic cell lines [1].
HDAC3 inhibitor is an allosteric inhibitor of histone deacetylase 3 (HDAC3; Ki = 0.16 nM). It is selective for HDAC3 over HDAC1 and HDAC2 (IC50s = 0.95, 11.81, and 95.45 nM, respectively, using recombinant HDACs). In addition, it is selective for acute myeloid, monocytic, and lymphoblastic leukemia cell lines (EC50s = 36.37, 76.64, and 151.7 nM, respectively) over chronic myeloid, acute promyelocytic, and acute lymphoblastic cells (EC50s = 2,160, >10,000, and >10,000 nM, respectively).
HDAC6-IN-3 (Compound 14) is a potent anti-prostate cancer agent that acts as an orally active inhibitor of HDAC6. It has IC50 values ranging from 0.02-1.54 μM for HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10. Additionally, HDAC6-IN-3 also demonstrates effective inhibition of MAO-A (IC50 = 0.79 μM) and LSD1 [1].
CAY10722 is an inhibitor of sirtuin 3 (SIRT3), a class III HDAC (71% inhibition at 200 μM). SIRT3 is involved in modulating metabolic homeostasis as a NAD+-dependent protein deacetylase in the mitochondria. SIRT3 functions as either an oncogene or tumor suppressor, depending on cancer cell type. High SIRT3 expression in patient-derived esophageal cancer tissues is associated with shorter survival and, in mice, downregulation leads to a lower tumor load. In contrast, low SIRT3 expression in patient-derived breast cancer cells is correlated with shorter survival.
MHY219 is a novel HDACinhibitor. MHY219 induces apoptosis via up-regulation of androgen receptor expression in human prostate cancer cells. MHY219 was shown to enhance the cytotoxicity on DU145 cells (IC50, 0.36 μM) when compared with LNCaP (IC50, 0.97 μM) and PC3 cells (IC50, 5.12 μM). MHY219 showed a potent inhibition of total HDAC activity when compared with SAHA. MHY219 increased histone H3 hyperacetylation and reduced the expression of class I HDACs (1, 2 and 3) in prostate cancer cells. MHY219 effectively increased the sub-G1 fraction of cells through p21 and p27 dependent pathways in DU145 cells. MHY219 significantly induced a G2/M phase arrest in DU145 and PC3 cells and arrested the cell cycle at G0/G1 phase in LNCaP cells. Furthermore, MHY219 effectively increased apoptosis in DU145 and LNCaP cells, but not PC3 cells, according to Annexin V/PI staining and Western blot analysis. These results indicate that MHY219 is a potent HDACinhibitor that targets regulating mu......
MPT0G211 mesylate is a powerful and selective HDAC6 inhibitor (IC50 = 0.291 nM), with high oral bioavailability. It exhibits remarkable selectivity for HDAC6 over other HDAC isoforms (>1000-fold selectivity). Additionally, MPT0G211 mesylate can effectively cross the blood-brain barrier. In preclinical studies using an Alzheimer's disease model, MPT0G211 mesylate has shown promising results in reducing tau phosphorylation and cognitive deficits. Furthermore, this compound exhibits anti-metastatic and neuroprotective effects, making it a potential candidate for anticancer interventions. [1] [2] [3].
Givinostat (ITF-2357) is a HDACinhibitor with an IC50 of 198 and 157 nM for HDAC1 and HDAC3, respectively. Givinostat (ITF2357) suppresses total LPS-induced IL-1β production robustly compared with the reduction by ITF3056. At 25, 50, and 100 nM, Givinostat reduced IL-1β secretion more than 70%. Givinostat (ITF-2357) suppresses the production of IL-6 in PBMCs stimulated with TLR agonists as well as the combination of IL-12 plus IL-18. IL-6 secretion decreases to 50% at 50 nM Givinostat, but at 100 and 200 nM, there is no reduction[1]. As shown by the CCK-8 assay, Givinostat (ITF-2357) inhibits JS-1 cell proliferation in a concentration-dependent manner. Treatment with Givinostat ≥500 nM is associated with significant inhibition of JS-1 cell proliferation (P<0.01). Also, the cell inhibition rate significantly differs between the group cotreated with Givinostat ≥250 nM plus LPS and the group without LPS treatment (same Givinostat concentration) (P<0.05)[2]. Givinostat (ITF2357) at 10 mg kg is used as a positive control and, as expected, reduced serum TNFα by 60%. Strikingly, pretreatment of ITF3056 starting at 0.1 mg kg significantly reduces the circulating TNFα by nearly 90%. To achieve a significant increase in serum IL-1β production, a higher dose of LPS is injected (10 mg kg), and blood is collected after 4 h. Similarly, when pretreated with lower doses of Givinostat (ITF-2357) (1 or 5 mg kg), there is a 22% reduction for 1 mg kg and 40% for 5 mg kg[1]. [1]. Li S, et al. Specific inhibition of histone deacetylase 8 reduces gene expression and production of proinflammatory cytokines in vitro and in vivo. J Biol Chem. 2015 Jan 23;290(4):2368-78. [2]. Wang YG, et al. Givinostat inhibition of hepatic stellate cell proliferation and protein acetylation. World J Gastroenterol. 2015 Jul 21;21(27):8326-39. [3]. Leoni F, et al. The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med. 2005 Jan-Dec;11(1-12):1-15.
Suberoylanilide hydroxamic acid (SAHA) is a class I and class II histone deacetylase (HDAC) inhibitor that binds directly to the catalytic site of the enzyme thereby blocking substrate access. SAHA-BPyne is a SAHA derivative with a benzophenone crosslinker and an alkyne tag intended to be used for profiling HDAC activities in proteomes and live cells. Such terminal alkyne groups can be used in linking reactions, known as click chemistry, characterized by high dependability and specificity of azide-alkyne bioconjugation reactions. SAHA-BPyne labels HDAC complex proteins both in proteomes at 100 nM and in live cells at 500 nM and demonstrates an IC50 value of ~3 μM for inhibition of HDAC activity in HeLa cell nuclear lysates in an HDAC activity assay.