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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.
Home » Cores » Informatics

The key deliverables of the MLPCN are public data of high quality, published to PubChem, and supporting chemical probe development.  This mission requires two essential components, an Operational Environment for data management and QA, and a Knowledge Environment facilitating efficient chemical probe optimization. The Scripps Center has built these on a comprehensive production scale and will make key tools available broadly to maximize the impact of the MLPCN effort.

Our operational infrastructure (pictured below) includes chemical structure registration with application and user business rules, flexible sample and plate logistics, and assay protocol and assay data management systems. These systems are integrated with our laboratory automation infrastructure to efficiently process HTS screening campaigns.  Key integration components are Plato and Nightwatch.  These allow querying and synchronizing plates on the Kalypsys system with the Plate Manager database. Hit picking functionality takes hit lists in various formats and generates optimized TECAN input files and creates the corresponding plates in the Plate Manager database. Plate transformation functionality includes creating of ‘cherry picking’ plates and ‘dose response’ plates.

Informatics Workflow

Figure 1.  Overview of informatics environment (Click image to expand). A) MLSMR external compound repository provides chemical structure, plate, and well shipment data, which are pre-processed via Pipeline Pilot (PP) protocols B) and registered into the MDL-based central compound registration system C). After association with corporate compound and batch IDs, plate information is registered into the MDL-based Plate logistics system D), which is integrated via an in-house developed web-based system (Plato) E) with our uHTS robotics system (Kalypsys) F). Screening progress is monitored via in-house developed software (NightWatch) G) and loaded into MDL Assay Explorer H). Assay results are processed and published via automated PP protocols I) into Pubchem J). Released screening data is picked up via PP integration K) and aggregated by metrics into the central data warehouse (Oasis) L). Oasis retrieves structures via the MDL chemical registration database C). Oasis can be queried via ISIS RAF or our in-house ChemInfo portal (not shown) or PP Webport M) to produce SAR reports M). As an example of integration of discovery systems, structures from the MDL database are loaded into LeadScope O) via a PP structure loader N). Pubchem MLSMR structures J) are kept updated in LeadScope using the structure loader. Project-specific data is loaded via PP processes N) from Oasis L) into Leadscope O). After data analysis in Leadscope results are reported using the PP reporting collection P) into interactive heat map and SAR reports Q).


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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