G-protein-coupled receptors (GPCRs) are thought to represent the largest gene family in the human genome, with approximately 800 members (300-400 of which are believed to be involved in olfactory, taste, or pheromone sensation). GPCR systems play key roles in almost every aspect of physiology and therefore have broad relevance to human disease. Moreover, GPCRs have proven to be particularly amenable to modulation by small molecule ligands, which makes them excellent therapeutic targets for a number of diseases.
Many GPCR proteins already have known ligands (endogenous or otherwise), but many are “orphan” GPCRs with no known ligands. At GNF, we have developed considerable expertise in the area of GPCR biology. In addition to traditional drug discovery approaches targting GPCRs, our scientists are leveraging GNF’s functional genomics expertise (e.g., siRNA libraries) to probe the role of GPCRs in cellular signaling pathways (leading to identification of novel GPCR targets) and are also applying advanced automation technologies to enable broad-based parallel approaches to identifying new ligands for GPCRs. Such ligands can then serve as starting points for new drug discovery programs or enable reverse pharmacology to understand the role of various GPCRs (orphan or otherwise) in mammalian biology.