Journal
EXPERT OPINION ON DRUG DISCOVERY
Volume 11, Issue 10, Pages 1017-1025Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2016.1227316
Keywords
Chemical proteomics; small molecule target identification; target deconvolution; phenotypic screening; chemical biology; mass spectrometry; thermal proteome profiling; DARTS; SPROX; UPT; CETSA
Categories
Ask authors/readers for more resources
Introduction: Drug discovery efforts across the globe are chasing new drug targets and novel mechanisms of action. To support the identification of novel mechanisms of action, phenotype-based drug screening has significantly increased over the last decade. Along with the rise in phenotypic screening, methods and technologies that can help to identify drug targets of phenotypically screened 'hits' have also evolved significantly. Areas covered: This article provides an overview of successful examples, limitations and advances in small-molecule target identification methodologies. Primarily, the methods are described, where small-molecules without derivatization are used as test-molecules for identifying their direct binding protein partners, the targets, in detail. A brief discussion of other affinity chromatography coupled mass-spectrometry based target identification methods are also presented for comparative appreciation of label-free methods. Expert opinion: Label-free methods do not require (a) extensive structure activity analysis of phenotypically screened 'hits' and (b) preparation of tool compounds or target capturing probes for target identification. These methods are significantly shortening the time required for the identification and the downstream validation of targets and hence are gaining popularity as the method of choice for target identification.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available