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.
| Molecular Weight | 579.27 |
| Formula | C14H20BrN4O12PS |
| CAS Number | 851627-62-8 |
| Solubility (25°C) | DMSO 90 mg/mL Water 30 mg/mL (ultrasonic and warming) |
| Storage | -80°C, protect from light, sealed |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| 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.
[2] Simone Fulda. Blood. Biomarker of sensitivity to PR-104 in leukemia
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