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Receptos Scientists Publish Determination of a High Resolution Sphingosine 1-Phosphate Receptor 1 Structure in Science
Date:2/16/2012

onduct novel drug screening assays and study dynamic conformational changes to receptor topography that allow rational drug design for high-value GPCR targets. These collaborators include Eli Lilly, Ono Pharmaceutical and Janssen Pharmaceuticals.

Advancements in the technology, as well as in proprietary drug discovery and development programs at Receptos, have resulted in a patent estate comprising twelve patent applications, seven of which are directed to small molecule composition of matter and four of which support the technology platform, including novel reagents to enable crystallography. The Receptos scientific management team has broad experience in the development and registration of therapeutics including rituximab, targretin, panretin, belatacept, abatacept, omalizumab, and others.

About the S1P1 Target and Utilization of the S1P1 Structure

The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein–coupled sphingosine 1-phosphate receptors. Activation of the S1P1 receptor through exogenous ligands, both physiological and pharmacological, results in significant inhibition of lymphocyte re-circulation. This physiological effect was leveraged in the development of the nonselective S1P receptor agonist prodrug fingolimod (GILENYA®), approved in 2010 for the clinical treatment of relapsing-remitting multiple sclerosis. The high resolution crystal structure of the sphingosine 1-phosphate receptor 1 has revealed the architecture of the ligand binding pocket and extracellular region providing insights into the molecular interactions associated with binding and signaling of diverse S1P ligands. In combination with mutagenesis and signaling studies, Receptos has pinpointed regions in the binding pocket responsible for driving interactions within S1P ligand classes, and prioritized drug candidates acc
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