PR-104 is a drug from the class of hypoxia-activated prodrugs (HAPs),[1] which is being researched as a potential anti-cancer therapeutic agent.

It is a phosphate ester “pre-prodrug” that is rapidly converted to the HAP PR-104A in the body.

PR-104A is in turn metabolised to reactive nitrogen mustard DNA crosslinking agents in hypoxic tissues such as found in solid tumours.

[2][3][4] Following initial clinical studies,[5][6] it was discovered that PR-104A is also activated by the enzyme AKR1C3, independently of hypoxia.

[7] Hypoxia in the bone marrow of patients with leukaemia,[8][9] and high activity of AKR1C3 in some leukaemia subtypes [10][11][12] has led to interest in clinical trials of PR-104 in relapsed refractory acute leukaemias.