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PR-104

Cat. No. M25447
PR-104 Structure
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Biological Activity

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.

Chemical Information
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
Conversion of different model animals based on BSA (PMID: 27057123)
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.

References

[1] 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

[2] Simone Fulda. Blood. Biomarker of sensitivity to PR-104 in leukemia

[3] Maria R Abbattista, et al. Cancer Biol Ther. Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib in hepatocellular carcinoma

[4] Mark J McKeage, et al. BMC Cancer. PR-104 a bioreductive pre-prodrυg combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours

[5] Ghassan K Abou-Alfa, et al. Cancer Chemother Pharmacol. PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma

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