Antitumor agent-76 (Compound TP-P1) 是一种具有口服活性的、快速释放、水溶性的 Triptolide (HY-32735) 前药，具有抗癌活性。
| 生物活性 | Antitumor agent-76 (Compound TP-P1) is an orally active, rapid-release and water-solubleTriptolide(HY-32735) prodrug with antitumor activity[1]. |
体外研究
(In Vitro) | Antitumor agent-76 (Compound TP-P1) shows good stability in aqueous solution, and the aqueous solubility (6.13 mg/mL in water) improved significantly compared to Triptolide[1].
Antitumor agent-76 (50 μg/mL) can be rapidly and completely converted into Triptolide within 30 min in rat plasma and within 45 min in human plasma. The concentration of Antitumor agent-76 has no significant effect on conversion rate[1].
Antitumor agent-76 (30-120 nM; 24 h) shows antiproliferative activities against acute myeloid leukemia (AML) cells without cytotoxicity towards normal cells[1].
Cell Proliferation Assay[1] | Cell Line: | THP-1 and MV-4-11 cells | | Concentration: | 30, 60, or 120 nM | | Incubation Time: | 24 h | | Result: | Showed antiproliferative activities with IC50s of 14.79±0.42 nM and 45.97±0.13 nM against THP-1 and MV-4-11 cells, respectively. |
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体内研究
(In Vivo) | Antitumor agent-76 (Compound TP-P1) (0-1.2 mg/kg; i.p.; daily for 28 days) inhibits tumor cell growth, proliferation and induces tumor cell apoptosis in mouse THP-1 and MV-4-11 xenografts models[1].
Antitumor agent-76 (100, 300 μg/kg/day; i.g.; 11 days) dose-dependently inhibits tumor growth in mouse MV-4-11 xenograft models[1].
Antitumor agent-76 is easily hydrolyzed in liver microsomes due to the high content of esterase in liver. The half-life is short (T1/2=8.64 min) and the clearance rate is high[1].
Pharmacokinetic study of Antitumor agent-76 (Compound TP-P1) and triptolide on Sprague Dawley ratsa[1].
| Compd | dosageb
(mg/kg) | AUC(0-t)(h
ng/ml) | Tmax
(h) | VZ/F
(L/kg) | CLZ/F
(L/h/kg) | Cmax
(μg/L) | | Antitumor agent-76 | 1.6 | 60.46 | 0.50 | 37831.99 | 24563.25 | 23.53 |
aThe values presented are the mean values from three independent mice.
bDosed po (oral administration) was administered via oral gavage.
| Animal Model: | Male BALB/c Nude mice, THP-1 xenograft and MV-4-11 xenograft[1] | | Dosage: | 0.1, 0.3, 0.6, 1.2 mg/kg for THP-1 xenograft, 25, 50, 100 μg/kg for MV-4-11 xenograft | | Administration: | Intraperitoneal administration, daily for 28 days | | Result: | Significantly and dose-dependently inhibited the tumor growth in THP-1 xenografts, with an excellent tumor growth inhibitory rate (TGI) of 93.87% at the dosage of 100 μg/kg. Inhibited cell proliferation and induced cell apoptosis in tumor tissues. Also showed excellent antitumor activity in MV-4-11 xenograft models (25 μg/kg with a TGI of 54.3%), and the tumors achieved complete regression on day 12 at the dosage of 100 μg/kg. |
| Animal Model: | Sprague Dawley rats[1] | | Dosage: | 1.6 mg/kg | | Administration: | Oral administration (Pharmacokinetic Analysis) | | Result: | Exhibited an acceptable pharmacokinetic property. |
| 分子量 | | | Formula | | | CAS 号 | | | 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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