Aclacinomycin A (Aclarubicin) 是一种口服有效的蒽环类抗肿瘤的抗生素 (antibiotic)。Aclacinomycin A 是拓扑异构酶 (topoisomerase) I 和 II 的抑制剂。Aclacinomycin A 可抑制核酸的合成，特别是RNA的合成。Aclacinomycin A 可能抑制 26S 蛋白酶复合体以及泛素-ATP 依赖性蛋白水解。
| 生物活性 | Aclacinomycin A (Aclarubicin) is an orally active and potent anthracycline antitumorantibiotic. Aclacinomycin A is an inhibitor oftopoisomeraseIandII. Aclacinomycin A inhibits synthesis of nucleic acid, especiallyRNA. Aclacinomycin A might inhibit the 26S protease complex as well as the ubiquitin-ATP-dependent proteolysis[1][2][3]. |
| IC50& Target | Topoisomerase I | Topoisomerase II |
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体外研究
(In Vitro) | Aclacinomycin A (0-120 μM, 30 min) inhibits the ubiquitin-ATP-dependent proteolytic activity of rabbit reticulocytes in a dose-dependent manner, with an IC50of 52 μM. But it does not inhibit the ubiquitination[1].
Aclacinomycin A inhibits ubiquitin-ATP-dependent proteolysis after the conjugation of ubiquitin to proteins[1].
Aclacinomycin A (0-2.4 μM, 3 h) inhibits the topo II catalytic activity[2].
Aclacinomycin A (0-1.8 μM, 3 h) has negative effect on the proliferative rate of V79 and irs-2 cells[2].
Aclacinomycin A emits fluorescence and that human-cervical cancer HeLa cells exposed to Aclacinomycin A exhibits bright fluorescence signals in the cytoplasm when fluorescence microscopy was performed using the red filter (excitation 530-550 nm/emission 575 nm)[3].
Cell Viability Assay[2] | Cell Line: | V79 and irs-2 cells | | Concentration: | 0, 0.006, 0.12, 1.2, and 2.4 μM | | Incubation Time: | 3 h | | Result: | Inhibited the topo II catalytic activity in a dose-dependent manner. The loss of topo II catalytic activity in ACLA-treated cells was in all cases significant compared with non-treated cells. |
Cell Proliferation Assay[2] | Cell Line: | V79 and irs-2 cells | | Concentration: | 0, 0.12, 0.25, 0.37, 0.6, 1.2, 1.8 μM | | Incubation Time: | 3 h | | Result: | Showed a dose-dependent negative effect on the proliferative rate of V79 and irs-2 cells, but the reduction in surviving colonies was higher in the radiosensitive irs-2 cells for most of the ACLA doses tested. |
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体内研究
(In Vivo) | Aclacinomycin A (0.75-6 mg/kg, IP, daily) dose-dependently exhibits tumor growth in mice-based Leukemia P-388 model[4].
Aclacinomycin A (0.6-20 mg/kg, Orally, daily) exhibits an antitumor effect on leukemia L-1210[4].
Aclacinomycin A is very well absorbed in mice, rats, and dogs after its oral administration. The oral LD50(76.5 mg/kg) is about twice the iv LD50(35.6 mg/kg) in mice[4].
| Animal Model: | DBA/2, CDF1(BALB/c×DBA/2) mice with Leukemia P-388 (90-110 g)[4]. | | Dosage: | 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg | | Administration: | Intraperitoneal administration daily for 10 days starting 3 hr after transplantation. | | Result: | Inhibited tumor growth. |
| Animal Model: | CDF1mouse with Leukemia L-1210[4] | | Dosage: | 0.6 mg/kg, 1.25 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg | | Administration: | Orally, daily for days 1-9 | | Result: | Exhibited an antitumor effect on leukemia L-1210. |
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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. |
