| Description |
Antitumor agent-76 (Compound TP-P1) is an orally active, rapid-release and water-soluble Triptolide (HY-32735) prodrug with antitumor activity[1].
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| Related Catalog |
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| 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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| 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]. a b 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 23.53The values presented are the mean values from three independent mice. Dosed 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.
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| References |
[1]. Kang D, et al. Discovery of a novel water-soluble, rapid-release triptolide prodrug with improved drug-like properties and high efficacy in human acute myeloid leukemia. Eur J Med Chem. 2022 Sep 5;243:114694.
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