PARP inhibitors: polypharmacology versus selective inhibition

被引：66

作者：

Ekblad, Torun ^{[1
]}

Camaioni, Emidio ^{[2
]}

Schuler, Herwig ^{[1
]}

Macchiarulo, Antonio ^{[2
]}

机构：

[1] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden

[2] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06123 Perugia, Italy

来源：

FEBS JOURNAL | 2013年 / 280卷 / 15期

关键词：

ADP-ribosyltransferases; cancer; drug design; PARP; poly(ADP-ribose) polymerases; polypharmacology; promiscuity; selective inhibitors; selectivity; structure-based drug design; ADP-RIBOSE POLYMERASE; DNA-DAMAGE RESPONSE; POLY(ADP-RIBOSE) POLYMERASE; IN-VITRO; SECONDARY MUTATIONS; POTENT INHIBITORS; STRUCTURAL BASIS; TUMOR-CELLS; IDENTIFICATION; TEMOZOLOMIDE;

D O I：

10.1111/febs.12298

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3563 / 3575

页数：13

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