Pradefovir 是一种逆转录酶抑制剂，可能用于治疗慢性 HBV 感染。它也是阿德福韦的肝脏靶向前药。代谢激活后，它在人肝微粒体中转化为 PMEA（9-（2-膦酰基甲氧基乙基）腺嘌呤），K(m) 为 60 microM，最大代谢速率为 228 pmol/min/mg 蛋白质，以及内在的清除率约为 359 ml/min。

Pradefovir is a reverse transcriptase inhibitor potentially for treatment of chronic HBV infection. Pradefovir is also a liver-targeted prodrug of adefovir. After metabolic activation, Pradefovir was converted to PMEA (9-(2-phosphonylmethoxyethyl)adenine ) in human liver microsomes with a K(m) of 60 microM, a maximum rate of metabolism of 228 pmol/min/mg protein, and an intrinsic clearance of about 359 ml/min.

Pradefovir, a prodrug of PMEA, is under phase 2 clinical trial in China to evaluate its pharmacokinetic and pharmacodynamics after multiple-dose study, with adefovir dipivoxil and tenofovir disoproxil fumarate as positive control. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of pradefovir, PMEA and tenofovir in HBV patient serum. Serum samples were pretreated via simple protein precipitation with methanol and entecavir was used as internal standard. Chromatographic separation was carried out on a Synergi(?) fusion-RP column (150mm×4.6mm) by gradient elution with methanol and 0.1% formic acid in water (v/v) at a flow rate of 1mL/min. The analytes were detected in multiple reaction monitoring mode with positive ion electrospray ionization at m/z 424.1/151.0, 274.1/162.2, 288.1/176.1, and 278.1/152.2for pradefovir, PMEA, tenofovir and IS, respectively. The assays were validated according to current bioanalytical guidelines including specificity, linearity (2.0-500ng/mL for pradefovir and PMEA, 4.0-1000ng/mL for tenofovir), accuracy and precision, extraction recovery, matrix effect and stability. The validated method has been successfully applied to the pharmacokinetic study of pradefovir, adefovir dipivoxil and tenofovir disoproxil fumarate in a set of HBV patients[1].

625095-60-5

C17H19ClN5O4P

423.79

Remofovir;MB-6866;ICN-2001-3;帕拉德福韦;MB-06866;ICN-20013

DMSO:Soluble
Powder: -20°C for 3 years
In solvent: -80°C for 2 years