Ivaltinostat (CG-200745) 是一种口服有效的泛HDAC抑制剂，具有异羟肟酸部分，可在催化袋底部结合锌。Ivaltinostat 抑制组蛋白 H3 和微管蛋白的脱乙酰作用。Ivaltinostat 诱导p53的积累，促进 p53 依赖性反式激活，并增强 MDM2 和 p21 (Waf1/Cip1) 蛋白的表达。Ivaltinostat 可增强 Gemcitabine 耐药细胞对 Gemcitabine (HY-16138) 和 5-Fluorouracil (5-FU; HY-90006) 的敏感性。Ivaltinostat 诱导凋亡并具有抗肿瘤作用。
| 生物活性 | Ivaltinostat (CG-200745) is an orally active, potent pan-HDACinhibitor 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 ofMDM2and p21 (Waf1/Cip1) proteins. Ivaltinostat enhances the sensitivity of Gemcitabine-resistant cells to Gemcitabine (HY-16138) and 5-Fluorouracil (5-FU; HY-90006). Ivaltinostat inducesapoptosisand has anti-tumour effects[1][2][3][4]. |
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体外研究
(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].
Cell Proliferation Assay[4] | Cell Line: | Calu6 cells | | Concentration: | 0-10 μM | | Incubation Time: | 48 hours | | Result: | Reduced the cell proliferation to 40% of untreated cells. |
Cell Cycle Analysis[4] | Cell Line: | Calu6 cells | | Concentration: | 3 μM | | Incubation Time: | 1, 8, 12, 24 hours | | Result: | Increased significantly cell proportion in G2/M phase (69%). |
Western Blot Analysis[4] | Cell Line: | Calu6 cells | | Concentration: | 0-10 μM | | Incubation Time: | 1, 4, 8, 12, 24 hours | | Result: | Increased the acetylation of histone H3 and H4 at various sites in a time-dependent manner. |
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体内研究
(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].
| Animal Model: | Male 8-week-old C57BL/6 J mice weighing 20~22 g of unilateral ureteral obstruction (UUO)[5] | | Dosage: | 30 mg/kg | | Administration: | PO; daily; for 7 days | | Result: | Attenuated oxidative stress, inflammatory cytokines and adhesion molecules in UUO kidneys. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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