KRA-533 是一种有效的KRAS激动剂。KRA-533 与 KRAS 蛋白中的 GTP/GDP binding pocket 结合，防止 GTP 切割，导致 GTP 结合 KRAS 的组成性活性积累，触发癌细胞中凋亡和自噬细胞死亡途径。
| 生物活性 | KRA-533 is a potentKRASagonist. KRA-533 binds to the GTP/GDP binding pocket in the KRAS protein to prevent GTP cleavage, resulting in the accumulation of constitutively active GTP-bound KRAS that triggers bothapoptoticandautophagiccell death pathways incancercells. |
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体外研究
(In Vitro) | KRA-533 (10 μM; 48 hours; HCC827 cells) enhances KRAS activity to a greater extent[1].
KRA-533 (0~15 μM; 48 hours; H157 cells) enhances KRAS activity in a dose-dependent manner, which is associated increased levels of pERK, ratio of active caspase 3/procaspase 3 and PARP cleavage, leading to apoptotic cell death[1].
KRA-533 (10 μM; 10 days; H292 cells) mediates cell growth suppression than those without KRAS mutation. KRA-533 (5~15 μM) can directly bind to WT, G12C, G12D and G13D mutant KRAS proteins. KRA-533 activates WT KRAS to increase its activity in a dose-dependent manner. KRA-533 further enhances the activities of active KRAS mutants[1].
Western Blot Analysis[1] | Cell Line: | HCC827 cells | | Concentration: | 10 μM | | Incubation Time: | 48 hours | | Result: | Enhanced KRAS activity to a greater extent. |
Apoptosis Analysis[1] | Cell Line: | H157 cells | | Concentration: | 0~15 μM | | Incubation Time: | 48 hours | | Result: | Enhanced KRAS activity in a dose-dependent manner, which was associated increased levels of pERK, ratio of active caspase 3/procaspase 3 and PARP cleavage, leading to apoptotic cell death. |
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体内研究
(In Vivo) | KRA-533 (0~30 mg/kg; i.p.; 28 days) suppresses tumor growth in a dose-dependent manner in lung cancer mutant KRAS xenografts and induces apoptosis and autophagy in tumor tissues in a dose-dependent manner[1].
KRA-533 shows optimal therapeutic index between 7.5 mg/kg and 30 mg/kg doses[1].
| Animal Model: | Nu/Nu nude mice (mutant KRAS xenografts)[1] | | Dosage: | 0~30 mg/kg | | Administration: | i.p.; 28 days | | Result: | Suppressed tumor growth in a dose-dependent manner in lung cancer mutant KRAS xenografts and induced apoptosis and autophagy in tumor tissues in a dose-dependent manner. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 250 mg/mL(795.72 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.1829 mL | 15.9144 mL | 31.8289 mL | | 5 mM | 0.6366 mL | 3.1829 mL | 6.3658 mL | | 10 mM | 0.3183 mL | 1.5914 mL | 3.1829 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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