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ID: ALA5257139
Journal: ACS Med Chem Lett
Title: Synthesis of Veliparib Prodrugs and Determination of Drug-Release-Dependent PARP-1 Inhibition.
Authors: Borgini M, Wipf P.
Abstract: Poly(ADP-ribose) polymerase (PARP) plays a key role in repairing DNA damage, and several PARP inhibitors have been approved as treatments in BRCA1/2 mutated breast and ovarian cancers. Mounting evidence also supports their application as neuroprotective agents since PARP overactivation compromises the mitochondrial homeostasis by consumption of NAD+ reserves, leading to an increase in reactive oxygen and nitrogen species and a spike in intracellular Ca2+ levels. Herein, we present the synthesis and preliminary evaluation of new mitochondria-targeting PARP inhibitor prodrugs of (±)-veliparib, with the goal to advance potential neuroprotective properties without impairing the repair of damaged DNA in the nucleus.
CiteXplore: 37197461