Journal
EXPERT OPINION ON DRUG DISCOVERY
Volume 18, Issue 5, Pages 505-513Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2023.2199979
Keywords
Chemical probes; drug discovery; open science; solute carriers; ubiquitination; targeted protein degradation
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The rational development of new therapeutics requires a thorough understanding of how aberrant signaling affects cellular homeostasis and causes human disease. Chemical probes are powerful tools for drug discovery that have led to fundamental insights into biological processes and have paved the way for the development of first-in-class drugs.
Introduction: The rational development of new therapeutics requires a thorough understanding of how aberrant signalling affects cellular homeostasis and causes human disease. Chemical probes are tool compounds with well-defined mechanism-of-action enabling modulation of, for example, domain-specific protein properties in a temporal manner, thereby complementing other target validation methods such as genetic gain- and loss-of-function approaches.Areas covered: In this review, the authors summarize recent advances in chemical probe development for emerging target classes such as solute carriers and ubiquitin-related targets and highlight open resources to inform and facilitate chemical probe discovery as well as tool compound selection for target validation and phenotypic screening.Expert opinion: Chemical probes are powerful tools for drug discovery that have led to fundamental insights into biological processes and have paved the way for the development of first-in-class drugs. Open resources can inform on various aspects of chemical probe development and provide access to data and recommendations on use of chemical probes to catalyse collaborative science and help accelerate drug target identification and validation.
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