Target identification and mechanism of action in chemical biology and drug discovery

• Published in: Nature chemical biology Vol. 9; no. 4; pp. 232 - 240
• Main Authors: Schenone, Monica, Dančík, Vlado, Wagner, Bridget K, Clemons, Paul A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2013; Nature Publishing Group
• Subjects: 631/154; 631/92/555; 631/92/609; Animals; Biochemical Engineering; Biochemistry; Biology; Biomarkers, Pharmacological - chemistry; Biomarkers, Pharmacological - metabolism; Bioorganic Chemistry; Cell Biology; Chemicals; Chemistry; Chemistry/Food Science; Drug Discovery; Drug Evaluation, Preclinical; Drug therapy; High-Throughput Screening Assays; Humans; Isotope Labeling; Mass Spectrometry; Molecular Targeted Therapy; Molecules; Phenotype; Proteins; Reverse Genetics; review-article; RNA Interference; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Small Molecule Libraries - chemistry; Small Molecule Libraries - metabolism; Small Molecule Libraries - pharmacology; Validation Studies as Topic
• ISSN: 1552-4450; 1552-4469
• DOI: 10.1038/nchembio.1199

Target-identification and mechanism-of-action studies have important roles in small-molecule probe and drug discovery. Biological and technological advances have resulted in the increasing use of cell-based assays to discover new biologically active small molecules. Such studies allow small-molecule action to be tested in a more disease-relevant setting at the outset, but they require follow-up studies to determine the precise protein target or targets responsible for the observed phenotype. Target identification can be approached by direct biochemical methods, genetic interactions or computational inference. In many cases, however, combinations of approaches may be required to fully characterize on-target and off-target effects and to understand mechanisms of small-molecule action.