High-Throughput Lead Finding and Optimisation for GPCR Targets
Driven by past successes and the detailed knowledge of signalling cascades and physiological processes, G-protein-coupled receptors are taking a prominent place in the portfolios of many pharmaceutical companies. To successfully address this target class, scientists need not only a good understanding of the specific receptor under investigation, but also the right tools from assay technology, reagent production to a hit-to-lead process that acknowledges the importance of parameters beyond potency and embraces the gain in knowledge of the last decade. This manuscripts attempts to summarise some of the changes and progress made across the pharmaceutical industry to design an efficient and effective strategy for finding and optimising small molecules modulating the activity of GPCRs.
KeywordsLead Optimisation Lead Finding Biological Screening Lead Selection Assay Technology
- Alanine A, Nettekoven M, Roberts E, Thomas AW (2003) Lead generation – enhancing the success of drug discovery by investing in the hit to lead process. Comb Chem High Through Screen 6:51–66Google Scholar
- Glasel JA (2004) Emerging concepts in GPCR research and their implications for drug discovery. Decision Res www.decisionresources.com. Cited 26 November 2006Google Scholar
- Hefti E, Bolten BM (2000) Advances in high throughput screening – do they lead to new drugs? Decision Resources, October 2003, www.decisionresources.com. Cited 26 November 2006Google Scholar
- Presland J (2005) Identifying novel modulators of G protein-coupled receptors via interaction at allosteric sites. Curr Opin Drug Disc Dev 8:567–576Google Scholar
- Young SS, Lam RLH, Welch WJ (2002) Initial compound selection for sequential screening. Curr Opin Drug Disc Dev 5:422–427Google Scholar