PR-104 is a novel hypoxia-activated DNA cross-linking agent with marked activity against human tumor xenografts, both as monotherapy and combined with radiotherapy and chemotherapy.
PR-104 (80 μM; 1 hour; SiHa cells) shows greater suppression of radiation-induced DNA single-strand breaks under hypoxic than aerobic conditions. PR-104 (100 μM; 1 hour; SiHa cells) results in phosphorylation of Ser139 of histone H2AX (gH2AX). PR-104 (0.266 mmol/kg; 18 h; SiHa cells) shows activity against hypoxic cells after irradiation.
|Solubility (25°C)||DMSO 90 mg/mL
Water 30 mg/mL (ultrasonic and warming)
|Storage||-80°C, protect from light, sealed|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
 Dean C Singleton, et al. Cancer Gene Ther. Bioreductive prodrυg PR-104 improves the tumour distribution and titre of the nitroreductase-armed oncolytic adenovirus ONYX-411NTR leading to therapeutic benefit
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