Ivaltinostat

Ivaltinostat (CG-200745) is an orally active, potent pan-HDAC inhibitor which has the hydroxamic acid moiety to bind zinc at the bottom of catalytic pocket. Ivaltinostat inhibits deacetylation of histone H3 and tubulin. Ivaltinostat induces the accumulation of p53, promotes p53-dependent transactivation, and enhances the expression of MDM2 and p21 (Waf1/Cip1) proteins. Ivaltinostat enhances the sensitivity of Gemcitabine-resistant cells to Gemcitabine (HY-16138) and 5-Fluorouracil (5-FU; HY-90006). Ivaltinostat induces apoptosis and has anti-tumour effects^[1][2][3][4]. In Vitro: Ivaltinostat (CG-200745; 0.01-100 μM; 48 hours) inhibits growth of prostate cancer cells (LNCaP, DU145 and PC3 cells). Ivaltinostat (1, 10 μM; 24, 48 hours) increases sub-G1 population, and activates caspase-9, -3 and -8^[2].
Ivaltinostat (0.001-100 μM; for 72?hours) inhibits proliferation of cholangiocarcinoma cells (IC50s of 0.63, 0.93, and 1.80?μM for SNU-1196, SNU-1196/GR, SNU-308 cells, respectively)^[3].
Ivaltinostat (0-10 μM; 48 hours) reduces the Calu6 cells proliferation to 40% of untreated cells^[4].
Ivaltinostat (3 μM; 1-24 hours) significantly increases Calu6 cells proportion in G2/M phase (69%)^[4].
Ivaltinostat (0-10 μM; 1-24 hours) treatment with low concentration significantly increases the acetylation of histone H3 and H4 in Calu6 cells at various sites in a time-dependent manner up to 24 hours after treatment^[4].
In Vivo: Ivaltinostat (CG-200745; p.o.; 30?mg/kg/day; for 7 days) attenuates oxidative stress, inflammatory cytokines, and adhesion molecules in UUO kidneys^[5].