KU 59403 是ATM的一个有效抑制剂，其对 ATM、DNA-PK 和 PI3K 的IC50值分别为 3 nM、9.1 μM 和 10 μM。
| 生物活性 | KU 59403 is a potentATMinhibitor, withIC50values of 3 nM, 9.1 μM and 10 μM forATM,DNA-PKandPI3K, respectively[1]. |
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体外研究
(In Vitro) | KU 59403 (1 μM) enhances VP-16 (1 μM) cytotoxicity to a similar extent in HCT116 and HCT116-N7 cells, and in the p53 mutant SW620 cells and human breast cancer cell line, MDAMB-231, sensitisation is 11.9±4.7 and 3.8±1.8-fold respectively. Inhibition of IR-induced ATM activity by KU 59403 (1 μM) is approximately 50% in MDA-MB231 cells and >50% in HCT116 cells that have low ATM expression and activity[1].
Cell Viability Assay[1] | Cell Line: | LoVo, HCT116 and SW620 (human colon cancer), and U2OS (human osteosarcoma) and MDA-MB-231 (human breast cancer) cells. | | Concentration: | 1 μM. | | Incubation Time: | 16 hours. | | Result: | Had at least 1000 times greater specificity for ATM over other members of the PI3K family tested.
Enhanced camptothecin cytotoxicity in both cell lines with greater enhancement being observed in the LoVo compared to the SW620 cells.
Significantly enhanced the cytotoxicity of fixed concentrations of VP-16 (0.1 and 1 μM) or NSC 123127 (10 or 100 nM) in these cell lines, with greater enhancement of VP-16 in SW620 cells and of NSC 123127 in LoVo cells. |
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体内研究
(In Vivo) | KU59403 with a single daily dose of 12.5 mg/kg causes a significant sensitization[1].
Increasing the dose of KU59403 to 25 mg/kg given twice daily results in the greatest chemo-sensitisation with a 3-fold increase in BMY-40481-induced tumour growth delay in both SW620 and HCT116-N7 xenografts, in the absence of a significantly increased toxicity[1].
| Animal Model: | CD-1 nude miceimplanted with SW620 or HCT116-N7 human cancer cell lines at 1×107cells per animal s.c. (n=5 per group)[1]. | | Dosage: | 6, 12.5 and 25 mg/kg. | | Administration: | I.P. twice daily (0 and 4 hours) and12.5 mg/kgonce daily. | | Result: | Treatment with BMY-40481 alone causes a modest tumour growth delay of 4 days (time to RTV4=10.5 days). This delay is extended to 8.5 days when given with KU 59403 at 12.5 mg/kg i.p. twice daily for 5 days and 11.5 days (time to RTV4=18 days) when given with KU 59403 at 25 mg/kg i.p. twice daily for 5 days. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
