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Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation to Therapeutics

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 420))

Abstract

Over the last 60 years, poly-ADP-ribose polymerases (PARPs, 17 family members in humans) have emerged as important regulators of physiology and disease. Small-molecule inhibitors have been essential tools for unraveling PARP function, and recently the first PARP inhibitors have been approved for the treatment of various human cancers. However, inhibitors have only been developed for a few PARPs and in vitro profiling has revealed that many of these exhibit polypharmacology across the PARP family. In this review, we discuss the history, development, and current state of the field, highlighting the limitations and opportunities for PARP inhibitor development.

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Authors and Affiliations

  1. Program in Chemical Biology, Oregon Health & Science University, Portland, OR, 97210, USA

    Ilsa T. Kirby & Michael S. Cohen

  2. Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, 97210, USA

    Ilsa T. Kirby & Michael S. Cohen

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  1. Ilsa T. Kirby
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  2. Michael S. Cohen
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Correspondence to Michael S. Cohen .

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Editors and Affiliations

  1. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA

    Benjamin F. Cravatt

  2. Department of Chemistry, University of Virginia, Charlottesville, VA, USA

    Ku-Lung Hsu

  3. Department of Chemistry, Boston College, Chestnut Hill, MA, USA

    Eranthie Weerapana

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Kirby, I.T., Cohen, M.S. (2018). Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation to Therapeutics. In: Cravatt, B., Hsu, KL., Weerapana, E. (eds) Activity-Based Protein Profiling. Current Topics in Microbiology and Immunology, vol 420. Springer, Cham. https://doi.org/10.1007/82_2018_137

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