title: What is next for small-molecule drug discovery?
abstract: Humankind has been in the business of discovering drugs for thousands of years. At present, small-molecule drug design is based on specific macromolecular receptors as targets for inhibition or modulation. To this end, a number of clever approaches have evolved over time: computer-aided techniques including structure-activity relationships and synthesis, high-throughput screening, quantitative structure-activity relationships, hypotheses derived from ligand- and/or structure-based information and focused library approaches. In recent years, several alternative strategies have appeared in the form of the emerging paradigms of polypharmacology, systems biology and personalized medicine. These innovations point to key challenges and breakthroughs likely to affect the future of small-molecule drug discovery.
authors.affiliation: CADD/Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543, USA. arthur.doweyko@bms.com
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Doweyko
mesh_terms: D002986:Clinical Trials as Topic; D017076:Computer-Aided Design; D055808:Drug Discovery / Q000379:methods* / Q000639:trends*; D006801:Humans; D008519:Medicine, Traditional; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D057285:Precision Medicine; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship; D049490:Systems Biology
chemical_list: D010936:Plant Extracts; D054852:Small Molecule Libraries