72 (PB062) - Differential off-target pharmacology between the PARP inhibitor rucaparib and its major metabolite

Abstract

Background: Drug metabolites are generally more soluble, achieve lower concentrations in human plasma and can be excreted more easily than their parent drugs. Accordingly, drug metabolites are rarely characterized comprehensively in preclinical models and their on- and off-target activity is often overlooked. However, drug metabolites can play significant roles in the efficacy and safety of their parent dugs and help us explain clinical observations. Four PARP inhibitors have been approved by the FDA as cancer therapeutics, namely, olaparib, rucaparib, niraparib and talazoparib.