What is next for small-molecule drug discovery?
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Updated: Jun 3, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
Published on: May 16, 2021
Arthur M Doweyko1, Lidia M Doweyko
1CADD/Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543, USA. arthur.doweyko@bms.com
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.
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