title: PARP inhibitors: polypharmacology versus selective inhibition.
abstract: Inhibition of ADP-ribosyltransferases with diphtheria toxin homology (ARTD), widely known as the poly(ADP-ribose) polymerase (PARP) family, is a strategy under development for treatment of various conditions, including cancers and ischemia. Here, we give a brief summary of ARTD enzyme functions and the implications for their potential as therapeutic targets. We present an overview of the PARP inhibitors that have been used in clinical trials. Finally, we summarize recent insights from structural biology, and discuss the molecular aspects of PARP inhibitors in terms of broad-range versus selective inhibition of ARTD family enzymes.
authors.affiliation: Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Stockholm, Sweden.
authors.forename: Torun
authors.initials: T
authors.lastname: Ekblad
authors.forename: Emidio
authors.initials: E
authors.lastname: Camaioni
authors.forename: Herwig
authors.initials: H
authors.lastname: Schüler
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D002986:Clinical Trials as Topic; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D003606:Dacarbazine; C531549:rucaparib; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D000077204:Temozolomide
keywords: ADP-ribosyltransferases; PARP; cancer; drug design; poly(ADP-ribose) polymerases; polypharmacology; promiscuity; selective inhibitors; selectivity; structure-based drug design