G protein-coupled receptors (GPCRs) are proteins located on a cell's surface. These receptors play a key role in cell to cell communication by providing a mechanism by which a signal outside a cell can trigger a process inside the cell.

Our drug candidates have resulted from our GPCR-focused drug discovery technologies and capabilities, including Constitutively Activated Receptor Technology, or CART, our Melanophore technology and our overall approach to drug discovery and development. GPCRs are categorized as "known" when their naturally occurring, or native, ligands have been identified. Scientists have used molecular cloning in combination with the sequencing of the human genome to identify both additional receptor subtypes of known GPCRs as well as hundreds of novel GPCRs. These novel GPCRs are categorized as "orphan" GPCRs because their native ligands have not been identified. We believe both orphan and known GPCRs offer significant promise for the development of novel GPCR-based therapeutics.

Our drug discovery technologies allow us to simultaneously identify drug leads that act as receptor activators, or agonists, which increase the detected biological response, or act as receptor inhibitors, or antagonists, which decrease the detected response. We can also identify inverse agonists, which inhibit ligand-independent, as well as ligand-dependent, receptor activity. We use our drug discovery technologies to detect GPCRs that couple to major G protein classes. We believe our technologies are well-suited for studies of orphan receptors whose coupling parameters are unknown. We believe our technologies provide us with robust, reproducible, high-throughput and low-cost means for identifying and optimizing GPCR agonists, antagonists and inverse agonists, and are sensitive enough to detect the constitutive activity of many GPCRs.

We believe that our drug discovery technologies offer several key advantages for drug discovery, including:

• Eliminating the need to identify the native ligand for an orphan receptor;
• Enhancing the detection of, and allowing us to simultaneously identify, both receptor inhibitor and receptor activator drug leads;
• Allowing for the identification of drug leads that inhibit both ligand-independent and ligand-dependent activity; and
• Providing the ability to discover novel and improved therapeutics directed at known receptors.

(NOTE: This page was last updated: June 5, 2008.)