Apratoxin A 是一种蓝藻代谢物，通过诱导 G1 细胞周期停滞和凋亡级联反应来介导抗增殖活性。Apratoxin A 与 Hsp70/Hsc70 结合以促进 Hsp90 客户蛋白的降解。Apratoxin A 可以特异性结合 Sec61 复合体。
| 生物活性 | Apratoxin A, a cyanobacterial metabolite, mediates antiproliferative activity through the induction of G1 cell cycle arrest and anapoptoticcascade. Apratoxin A associates withHsp70/Hsc70to promote the degradation ofHsp90client proteins. Apratoxin A can specifically bind the Sec61 complex[1][2][3]. |
| IC50& Target[2][3] | |
体外研究
(In Vitro) | Apratoxin A (5, 50 nM; 24, 48 小时) 诱导 G1 细胞周期停滞和细胞凋亡。Apratoxin A 在酵母细胞中没有表现出任何生长抑制活性[1]。
Apratoxin A (50 nM; 1-24 小时) 抑制 STAT3 的 Tyr705 磷酸化[1]。
Cell Cycle Analysis[1] | Cell Line: | U2OS cells | | Concentration: | 5, 50 nM | | Incubation Time: | 24, 48 h | | Result: | Resulted in an accumulation of cells harboring 2N (diploid) content of chromo-somes , suggesting G1-phase cell cycle arrest.
Showed a complete block in cell cycle progression with 5 nM for 48 h. |
Apoptosis Analysis[1] | Cell Line: | U2OS cells | | Concentration: | 50 nM | | Incubation Time: | 0-48 h | | Result: | A sub-G1 population emerged 50 nM, suggesting cellular apoptosis.
Had 20-fold higher caspase-3 activity after 48 h. |
Western Blot Analysis[1] | Cell Line: | U2OS cells | | Concentration: | 50 nM | | Incubation Time: | 1, 4, 12, 24 h | | Result: | had no effect on phosphorylation of Ser727 , but strongly inhibited constitutive phosphorylation at Tyr705 of STAT3. |
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体内研究
(In Vivo) | Apratoxin A (0.5-1 mg/kg; 静脉给药; 每 7 天一次; BxPC-3 T1 模型 2 次; A549 模型 3 次) 具有剂量依赖性抗癌活性[2]。
Apratoxin A (1 mg/kg; 静脉注射) 具有高分布容积 (Vss=19.31 L/kg) 和中等半衰期 (11.57 小时)[2]。
| Animal Model: | 6-week old female NCr nu/nu mice with BxPC-3 T1 or A549 cells[1] | | Dosage: | 0.5, 0.75, 1 mg/kg | | Administration: | IV; every 7 days; for 2 total doses(BxPC-3 T1 study) or 3 doses (A549 study) | | Result: | For BxPC3 T1 model, both 1 mg/kg and 0.75 mg/kg were found to exceed the MTD with a treated versus vehicle control effect on tumor size (T/C ratio) of 53% and 41%, respectively. It induced severe body weight loss right after first dose in both 1 mg/kg and 0.75 mg/kg.
In the A549 model, 0.6 mg/kg, 0.5 mg/kg, and 0.4 mg/kg showed T/C ratios of 30%, 24%, and 41%, respectively. |
| Animal Model: | Athymic (NCr nu/nu) mice with A549 tumor cells[2] | | Dosage: | 1 mg/kg | | Administration: | IV | | Result: | Showed a high volume of distribution (Vss=19.31 L/kg) and moderate half-life (11.57 hours). |
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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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