January 28, 2011

A probe project executed by the Scripps Research Institute (TSRI), a funded center of the NIH Common Fund Molecular Libraries and Imaging Program (MLP), has become the program’s first to yield a drug candidate tested in humans. The initial probe compound resulting from the MLP efforts, an agonist of the sphingosine-1-phosphate receptor 1 (S1P1) and related molecules, was further developed outside of the MLP by TSRI and Receptos Inc., eventually resulting in administration to the first human subject in an FDA approved Phase 1 clinical safety study being undertaken by Receptos Inc. The clinical study has been initiated as a potential treatment for multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (brain and spinal cord). Patients with MS suffer damages to myelin, the material that surrounds and insulates nerve cells. There are approximately 250,000 to 350,000 people in the United States with MS diagnosed by a physician. MS is currently believed to be an immune-mediated disorder. Sphingosine-1-phospate (S1P) is a phospholipid released by platelets, mast and other cells. S1P stimulates at least five different G-protein coupled receptors (GPCRs), called the S1P receptor subtypes 1-5 (S1P1-5). These GPCRs mediate a number of biological responses. S1P1 plays a key role in the immune system, regulating lymphocyte egress from lymphoid tissues into the circulation. It is believed that S1P1 agonists induce T-cell sequestration in lymph nodes, diminishing their ability to reach distant sites and contribute to MS pathology, including inflammation and demyelination.

The mission of the Molecular Libraries Probe Production Centers Network (MLPCN) is to provide high-throughput screening and medicinal chemistry resources to the scientific community in order to identify small chemical probes to study the function of genes, cells, and biochemical pathways.  Although many MLP probes have been tested in in vivo studies (e.g., rat models), this is the first example of an MLP probe to have been further developed far enough along the drug discovery pipeline to be tested in humans, a landmark achievement for the program. The original 2007 probe report for the TSRI S1P1 agonist can be found here.