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 前药，具有抗癌活性。

Antitumor agent-76 (Compound TP-P1) is an orally active, rapid-release and water-soluble Triptolide prodrug with antitumor activity [1].

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 IC 50 s of 14.79±0.42 nM and 45.97±0.13 nM against THP-1 and MV-4-11 cells, respectively.

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 (T 1/2 =8.64 min) and the clearance rate is high [1]. Pharmacokinetic study of Antitumor agent-76 (Compound TP-P1) and triptolide on Sprague Dawley rats a [1]. Compd dosage b (mg/kg) AUC (0-t) (h ng/ml) T max (h) V Z/F (L/kg) CL Z/F (L/h/kg) C max (μg/L) Antitumor agent-76 1.6 60.46 0.50 37831.99 24563.25 23.53 a The values presented are the mean values from three independent mice. b 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.

2787593-12-6

C28H36ClNO10

582.04

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years