"目录号: HY-14842
Cell Cycle/DNA DamageEpigenetics-
Givinostat 是HDAC抑制剂。抑制HDAC1和HDAC3，IC50分别为 198 nM 和 157 nM。
HDAC
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生物活性
Description
Givinostat is aHDACinhibitor with anIC50of 198 and 157 nM forHDAC1andHDAC3, respectively.
IC50& Target
IC50: 198 nM (HDAC1), 157 nM (HDAC3)[1]
In Vitro
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 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 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].
In Vivo
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 ITF3056 (1 or 5 mg/kg), there is a 22% reduction for 1 mg/kg and 40% for 5 mg/kg[1].
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References
[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.