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PR-104 + gemcitabine

Development stage: Discontinued
Lead developer: Proacta
Modality: Small Molecules
Administration: Intravenous

Overview

PR-104 + gemcitabine is a combination therapy consisting of PR-104, a bioreductive pre-prodrug, and gemcitabine, a chemotherapeutic agent. PR-104 is rapidly hydrolyzed systemically to PR-104A, which is then activated in hypoxic cells via reduction by NADPH:cytochrome P450 oxidoreductase and other one-electron reductases, and by aldo-keto reductase 1C3 (AKR1C3) independently of oxygen. The activated metabolites (PR-104H and PR-104M) are reactive nitrogen mustards that crosslink DNA and cause cytotoxicity in cells. This combination was investigated in clinical trials for patients with advanced solid tumors.

Targets

DNA

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