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 » Publications » Screening Publications
Screening Publications
Conn PM, Smith E, Hodder P, Janovick JA, Smithson DC.
High Throughput Screen for Pharmacoperones of the Vasopressin Type 2 Receptor.

 
Karapetyan YE, Sferrazza GF, Zhou M, Ottenberg G, Spicer T, Chase P, Fallahi M, Hodder P, Weissmann C, Lasmézas CI.
Unique drug screening approach for prion diseases identifies tacrolimus and astemizole as antiprion agents.

1 Google Scholar Citation
 
Khan SH, Awasthi S, Guo C, Goswami D, Ling J, Griffin PR, Simons SS Jr, Kumar R.
Binding of the N-terminal region of coactivator TIF2 to the intrinsically disordered AF1 domain of the glucocorticoid receptor is accompanied by conformational reorganizations.

4 Google Scholar Citations
 
Cahalan SM, Gonzalez-Cabrera PJ, Nguyen N, Guerrero M, George Cisar EA, Leaf NB, Brown SJ, Roberts E, Rosen H.
S1P1 Receptor Upregulation and Amelioration of Experimental Autoimmune Encephalomyelitis by an S1P1 Antagonist.

2 Google Scholar Citations
 
Pascal BD, Willis S, Lauer JL, Landgraf RR, West GM, Marciano D, Novick S, Goswami D, Chalmers MJ, Griffin PR.
HDX workbench: software for the analysis of H/D exchange MS data.

7 Google Scholar Citations
 
Adibekian A, Martin BR, Chang JW, Hsu KL, Tsuboi K, Bachovchin DA, Speers AE, Brown SJ, Spicer T, Fernandez-Vega V, Ferguson J, Hodder PS, Rosen H, Cravatt BF.
Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probes.

10 Google Scholar Citations
 
Sarkisyan G, Cahalan S, Gonzalez-Cabrera P, Leaf N, Rosen H.
Real-time differential labeling of blood, interstitium and lymphatic and single-field analysis of vasculature dynamics in vivo.

2 Google Scholar Citations
 
Gonzalez-Cabrera PJ, Cahalan SM, Nguyen N, Sarkisyan G, Leaf NB, Cameron MD, Kago T, Rosen H.
S1P(1) receptor modulation with cyclical recovery from lymphopenia ameliorates mouse model of multiple sclerosis.

9 Google Scholar Citations
 
Rillahan CD, Brown SJ, Register AC, Rosen H, Paulson JC.
High-throughput screening for inhibitors of sialyl- and fucosyltransferases.

5 Google Scholar Citations
 
Guerrero M, Urbano M, Zhao J, Crisp M, Chase P, Hodder P, Schaeffer MT, Brown S, Rosen H, Roberts E.
Discovery, design and synthesis of novel potent and selective sphingosine-1-phosphate 4 receptor (S1P?-R) agonists.

3 Google Scholar Citations
 
Peatey CL, Spicer T, Hodder P, Trenholme KR, Gardiner DL.
A high-throughput assay for the identification of drugs against late-stage Plasmodium falciparum gametocytes.

  14 Google Scholar Citations
 
Iwasaki A, Medzhitov R.
A new shield for a cytokine storm.

7 Google Scholar Citations
 
Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F, Martinborough E, Peach R, Oldstone MB, Rosen H.
Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection.

94 Google Scholar Citations
 
Urbano M, Guerrero M, Zhao J, Velaparthi S, Schaeffer MT, Brown S, Rosen H, Roberts E.
SAR analysis of innovative selective small molecule antagonists of sphingosine-1-phosphate 4 (S1P?) receptor.

6 Google Scholar Citations
 
Walsh KB, Teijaro JR, Wilker PR, Jatzek A, Fremgen DM, Das SC, Watanabe T, Hatta M, Shinya K, Suresh M, Kawaoka Y, Rosen H, Oldstone MB.
Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus.

40 Google Scholar Citations
 
Baillargeon P, Scampavia L, Einsteder R, Hodder P
Monitoring of HTS Compound Library Quality via a High-Resolution Image Acquisition and Processing Instrument

2 Google Scholar Citations
 
Chalmers MJ, Busby SA, Pascal BD, West GM, Griffin PR.
Differential hydrogen/deuterium exchange mass spectrometry analysis of protein-ligand interactions.

26 Google Scholar Citations
 
Willis S, Griffin PR.
Mutual information identifies sequence positions conserved within the nuclear receptor superfamily: approach reveals functionally important regions for DNA binding specificity.

 
Istrate MA, Spicer TP, Wang Y, Bernard JA, Helvering LM, Bocchinfuso WP, Richardson TI, Zink R, Kumar N, Montrose-Rafizadeh C, Dodge J, Hodder P, Griffin PR.
Development of an HTS-Compatible Assay for Discovery of ROR{alpha} Modulators Using AlphaScreen(R) Technology.

 
Vidovic D., Busby S.A., Griffin P.R., Schürer S.C.
A Combined Ligand- and Structure-Based Virtual Screening Protocol Identifies Submicromolar PPAR? Partial Agonists

14 Google Scholar Citations
 
Doghman M, Madoux F, Hodder P, Lalli E.
Identification and characterization of steroidogenic factor-1 inverse agonists.

2 Google Scholar Citations
 
Weerapana E, Wang C, Simon GM, Richter F, Khare S, Dillon MB, Bachovchin DA, Mowen K, Baker D, Cravatt BF.
Quantitative reactivity profiling predicts functional cysteines in proteomes.

151 Google Scholar Citations
 
Madoux F, Simanski S, Chase P, Mishra JK, Roush WR, Ayad NG, Hodder P.
An ultra-high throughput cell-based screen for wee1 degradation inhibitors.

5 Google Scholar Citations
 
Chalmers MJ, Pascal BD, Willis S, Zhang J, Iturria SJ, Dodge JA, Griffin PR.
Methods for the Analysis of High Precision Differential Hydrogen Deuterium Exchange Data.

12 Google Scholar Citations
 
Knuckley B, Jones JE, Bachovchin DA, Slack J, Causey CP, Brown SJ, Rosen H, Cravatt BF, Thompson PR.
A fluopol-ABPP HTS assay to identify PAD inhibitors.

16 Google Scholar Citations
 
Noël R, Song X, Jiang R, Chalmers MJ, Griffin PR, Kamenecka TM.
Efficient methodology for the synthesis of 3-amino-1,2,4-triazoles.

7 Google Scholar Citations
 
Dai SY, Burris TP, Dodge JA, Montrose-Rafizadeh C, Wang Y, Pascal BD, Chalmers MJ, Griffin PR.
Unique Ligand Binding Patterns Between Estrogen Receptor and Revealed by Hydrogen/Deuterium Exchange.

24 Google Scholar Citations
 
Stephan C. Schürer, Steven J. Brown, Pedro Gonzales Cabrera, Marie-Therese Schaeffer, Jacqueline Chapman, Euijung Jo, Peter Chase, Tim Spicer,  Peter Hodder and Hugh Rosen.
Ligand-binding pocket shape differences between S1P1 and S1P3 determine efficiency of chemical probe identification by uHTS.

34 Google Scholar Citations
 
A.S. Don, H. Rosen.
A fluorescent plate reader assay for ceramide kinase.

9 Google Scholar Citations
 
Lauer-Fields JL, Spicer TP, Chase PS, Cudic M, Burstein GD, Nagase H, Hodder P, Fields GB.
Screening of potential a disintegrin and metalloproteinase with thrombospondin motifs-4 inhibitors using a collagen model fluorescence resonance energy transfer substrate.

11 Google Scholar Citations
 
Thomas Schröter, Dmitriy Minond, Amiee Weiser, Chinh Dao, Jeff Habel, Timothy Spicer, Peter Chase, Pierre Baillargeon, Louis Scampavia, Stephan Schürer, Caty Chung, Chris Mader, Mark Southern, Nick Tsinoremas, Philip LoGrasso and Peter Hodder.
Comparison of Miniaturized Time-Resolved Fluorescence Resonance Energy Transfer and Enzyme-Coupled Luciferase High-Throughput Screening Assays to Discover Inhibitors of Rho-Kinase II (ROCK-II).

32 Google Scholar Citations
 




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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