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  1. Seminar at MSBoston 2014:  Phase 2 results of the RADIANCE trial...
  2. MS Drug Discovered at TSRI Is Safe and Effective in Phase II Study   
  3. Scripps Research Institute Scientists Identify First Potentially Effective Therapy for Human Prion Disease   
  4. Probe from SRIMSC Enters Phase II/III Clinical trials.   
  5. The Scripps Molecular Screening Center becomes the first to have 1000 AIDs in PubChem!   
  6. Receptos Scientists Publish Determination of a High Resolution S1P1 Structure in Science   
  7. NIH Common Fund researchers uncover structure of important target for drug design   
  8. NIH Research Matters: Designing New Diabetes Drugs   
  9. Discovery of a treatable mechanism for avoiding the deadly response to flu: North County Times, Eurekalert [1, 2]    
  10. Nature: Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand   
  11. Scripps Research and MIT scientists discover class of potent anti-cancer compounds    
  12. MLP Probe Project Leads to First in Human Studies    
  13. Business Wire:   Receptos Initiates Clinical Trials for S1P1 Agonist Program, Aimed at Multiple Sclerosis   
  14. Nature:   Quantitative reactivity profiling predicts functional cysteines in proteomes.

  15. Nature:   Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARc by Cdk5.
  16. Discovery and optimization of chemical probes to define important molecular signals in medicine.
  17. Nature Reviews Drug Discovery article:   Chemical modulators of S1P receptors as barrier-oriented therapeutic molecules.
  18. Nature Chemical Biology article: S1P1 signaling just keeps going and going and going…
  19. Nature Biotechnology article:   Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes.
Center Description

The goal of the MLPCN is to integrate high-throughput chemical approaches with state-of-the art genetics (cellular, molecular and in vivo biology in a multi-disciplinary effort to discover of proof-of-concept (POC) molecular probes for cell and in vivo systems. Probes help transform biomedical advances to impact on public health and quality of life.

Production capacity at The Scripps Center in the pilot MLSCN phase was demonstrated by publishing >68 assays in PubChem, optimizing POC probes for 5 molecular targets and peer-reviewed publication of probes with low nanomolar potency, selectivity, and in vivo efficacy, to define novel biological and therapeutic targets. The Center sustained full production capabilities for assay development and for uHTS implementation in 1536-well format (>20/year). >80 data sets were published in PubChem at a rate of 2 full library assays/month. In the past 12 months alone, 27 HTS campaigns including 20 primary cell-based screens) for 18 molecular targets in 8 different target classes, using 8 detection formats (and from 13 external PIs) published. Internal discovery projects were screened on a single compound library of >600,000, exceeding MLPCN requirements.

These data were achieved in well volumes of 5-10 ul at low cost. The Center spares NIH compound collection and controls cost using 2 ul of compound (solution per year for 24 primary screens, and requiring only 5 ul for hit-picks, reconfirmation and 10 point titrations. Formats include ion flux and GPCR assays, reporter gene, transcription factor and nuclear receptor assays, enzyme assays, protein-protein and protein-RNA interactions and phenotypic screens. The Center currently supports hit-to-probe chemical synthesis across 8 projects/year by resynthesis, chemi-informatics, medicinal chemistry, secondary and specificity assay implementation and screening pharmacokinetics/ metabolism studies for efficient probe optimization. The Center developed novel technologies for high throughput selectivity profiling across gene families and enzymes for optimizing target-selective probes.

This Comprehensive Center supports production discovery of POC probes for most target classes by meeting 3 Aims:

  1. Develop 25 assays/year to HTS readiness.
  2. Implement 25 uHTS screens/year at 300-500,000 individual compounds and publish quality-assured data to PubChem.
  3. Optimize screening hits to probes or POC in cells and/or in vivo for 10-15 programs/year.

The Center provides public data, tools and resources hat enhance the success of NIH Roadmap and impact on human health.


MS Drug Discovered at TSRI is Safe and Effective in Phase II Study


A compound discovered and synthesized in The Scripps Research Institute (TSRI) labs of Professors Hugh Rosen and Edward Roberts has provided positive results for safety and efficacy in Phase 2 clinical trials for relapsing multiple sclerosis, according to Receptos, the biopharmaceutical company developing the drug for approval by the US Food and Drug Administration.

“The Rosen and Roberts laboratories are very gratified to see these direct improvements in the lives of patients and families dealing with this debilitating illness,” said Rosen. “These data support our labs' approach at TSRI—that discovery of fundamental mechanisms in chemical biology provides the foundation for intelligent intervention in disease processes. Meeting the needs of patients and their families is our high calling in biomedical science.”

The drug candidate, RPC1063, was first discovered at TSRI from work in the National Institutes of Health (NIH) Molecular Libraries Initiative. The randomized, double-blind Phase 2 study assessed the efficacy, safety and tolerability of two orally administered doses of RPC1063 against placebo in 258 patients with relapsing multiple sclerosis across 77 sites in 13 countries. There was a highly statistically significant 86 percent reduction in MRI measures of disease activity.

A Phase 3 trial—a randomized, double-blind study involving 1,200 patients with relapsing multiple sclerosis—was launched in December 2013.

The detailed clinical abstract can be found  here.

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