References
- Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.
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- Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discov. 2011;10:507–519.
••This important article presents a comprehensive analysis of drug discovery during the 2000s, and makes a case for the importance of phenotype-based discoveries
- Moffatt JG, Rudolph J, Bailey D. Phenotypic screening in cancer drug discovery – past, present and future. Nat Rev Drug Discov. 2014;13:588–602.
- Payne DJ, Gwynn MN, Holmes DJ, et al. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2007;6:29–40.
•This presentation of a nearly decade-long effort toward antibacterial discovery highlights the limitations of taking a purely target-based approach toward drug discovery
- Guiguemde WA, Shelat AA, Garcia-Bustos JF, et al. Global phenotypic screening for antimalarials. Chem Biol. 2012;19:116–129.
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•This work outlines the authors’ recommended criteria in developing an effective phenotypic assay, and emphasizes the importance of using physiologically relevant material and readouts
- Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci USA. 2011;108:18843–18848.
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•This article summarizes the success stories that emerged from the NIH’s MLPCN screening program, and differentiates the characteristics of small-molecule probes and drugs
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- Schirle M, Jenkins JL. Identifying compound efficacy targets in phenotypic drug discovery. Drug Discov Today. 2015. DOI:10.1016/j.drudis.2015.08.001.
•This review provides a good overview of the many techniques necessary to understand small-molecule MoA
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- Lukens AK, Heidebrecht RW Jr, Mulrooney C, et al. Diversity-oriented synthesis probe targets plasmodium falciparum cytochrome b ubiquinone reduction site and synergizes with oxidation site inhibitors. J Infect Dis. 2015;211:1097–1103.
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- Plenge RM, Scolnick EM, Altshuler D. Validating therapeutic targets through human genetics. Nat Rev Drug Discov. 2013;12:581–594.
••This article discusses a genomics-based approach toward target validation and drug discovery, arguing that such human “experiments of nature” inspire more confidence in targets for therapeutics development
- Khurana V, Tardiff DF, Chung CY, et al. Toward stem cell-based phenotypic screens for neurodegenerative diseases. Nat Rev Neurol. 2015;11:339–350.
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- Esch EW, Bahinski A, Huh D. Organs-on-chips at the frontiers of drug discovery. Nat Rev Drug Discov. 2015;14:248–260.
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