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

Ilsa T. Kirby, Michael Cohen

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)211-231
Number of pages21
JournalCurrent Topics in Microbiology and Immunology
Volume420
DOIs
StatePublished - Jan 1 2019

Fingerprint

Adenosine Diphosphate
Polypharmacology
Poly(ADP-ribose) Polymerases
History
Therapeutics
Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)

Cite this

Small-Molecule Inhibitors of PARPs : From Tools for Investigating ADP-Ribosylation to Therapeutics. / Kirby, Ilsa T.; Cohen, Michael.

In: Current Topics in Microbiology and Immunology, Vol. 420, 01.01.2019, p. 211-231.

Research output: Contribution to journalArticle

@article{6dfa2647071549cc97ec95d9495ba765,
title = "Small-Molecule Inhibitors of PARPs: From Tools for Investigating ADP-Ribosylation to Therapeutics",
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.",
author = "Kirby, {Ilsa T.} and Michael Cohen",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/82_2018_137",
language = "English (US)",
volume = "420",
pages = "211--231",
journal = "Current Topics in Microbiology and Immunology",
issn = "0070-217X",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Small-Molecule Inhibitors of PARPs

T2 - From Tools for Investigating ADP-Ribosylation to Therapeutics

AU - Kirby, Ilsa T.

AU - Cohen, Michael

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85059827534&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059827534&partnerID=8YFLogxK

U2 - 10.1007/82_2018_137

DO - 10.1007/82_2018_137

M3 - Article

C2 - 30242511

AN - SCOPUS:85059827534

VL - 420

SP - 211

EP - 231

JO - Current Topics in Microbiology and Immunology

JF - Current Topics in Microbiology and Immunology

SN - 0070-217X

ER -