Research Topics
Genomes and Genes | Hugh RosenSummaryAffiliation: The Scripps Research Institute Country: USA Publications
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Publications
Sphingosine 1-Phosphate Receptor 1 (S1P1) Upregulation and Amelioration of Experimental Autoimmune Encephalomyelitis by an S1P1 AntagonistStuart M Cahalan
Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037
Mol Pharmacol 83:316-21. 2013....
Chemical approaches to the lysophospholipid receptorsHugh Rosen
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Prostaglandins Other Lipid Mediat 77:179-84. 2005..These developments, coupled with the availability of receptor knock-out mice, presage rapid progress in the field...
Modulating tone: the overture of S1P receptor immunotherapeuticsHugh Rosen
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Immunol Rev 223:221-35. 2008....- Egress: a receptor-regulated step in lymphocyte traffickingHugh Rosen
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Immunol Rev 195:160-77. 2003..This inhibition induces significant immunosuppression in models of transplantation and autoimmune tissue damage that may prove to be of clinical benefit... - Rapid induction of medullary thymocyte phenotypic maturation and egress inhibition by nanomolar sphingosine 1-phosphate receptor agonistHugh Rosen
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 100:10907-12. 2003..Inhibition of lymphocyte egress from thymus and lymph node can contribute synergistically to clinically useful immunosupression by disrupting recirculation of peripheral T cells... - Sphingosine 1-phosphate pathway therapeutics: a lipid ligand-receptor paradigmHugh Rosen
Department of Immunology and Committee for Advanced Human Therapeutics, The Scripps Research Institute, ICND 118 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Curr Opin Chem Biol 7:461-8. 2003..These approaches can potentially be extended to a broad, related family of G-protein-coupled receptors that share ligands and ligand similarities... - Tipping the gatekeeper: S1P regulation of endothelial barrier functionHugh Rosen
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Trends Immunol 28:102-7. 2007.... - Sphingosine 1-phosphate receptor signalingHugh Rosen
Departments of Chemical Physiology and Immunology and The Scripps Research Institute Molecular Screening Center, The Scripps Research Institute, La Jolla, CA 92037, USA
Annu Rev Biochem 78:743-68. 2009.... - Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like headgroup interactionsPedro J Gonzalez-Cabrera
Departments of Chemical Physiology and Immunology, Scripps Research Institute Molecular Screening Center, La Jolla, CA 92037, USA
Mol Pharmacol 74:1308-18. 2008..These data show that CYM-5442 activates S1P(1)-dependent pathways in vitro and to levels of full efficacy in vivo through a hydrophobic pocket separate from the orthosteric site of S1P binding that is headgroup-dependent... - S1P(1) receptor modulation with cyclical recovery from lymphopenia ameliorates mouse model of multiple sclerosisPedro J Gonzalez-Cabrera
Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA 92037, USA
Mol Pharmacol 81:166-74. 2012..S1P(1)-selective agonists that induce reversible lymphopenia while persisting in the CNS may be effective MS treatments... - Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethalityFrank Niessen
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
Blood 113:2859-66. 2009..Thus, the activating proteases and selectivity in coupling to S1P receptor subtypes determine vascular PAR1 signaling specificity in systemic inflammatory response syndromes in vivo... - Discovery, design and synthesis of novel potent and selective sphingosine-1-phosphate 4 receptor (S1P₄-R) agonistsMiguel Guerrero
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, United States
Bioorg Med Chem Lett 22:537-42. 2012..Remarkably, the molecules herein reported provide novel pharmacological tools to decipher the biological function and assess the therapeutic utility of the S1P(4)-R... - Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivoM Germana Sanna
Department of Immunology and The Scripps Research Institute Molecular Screening Center, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Chem Biol 2:434-41. 2006..Thus, chemical modulation reveals differences in S1P-S1P1 'set points' among tissues and highlights both mechanistic advantages (lymphocyte sequestration) and risks (pulmonary edema) of therapeutic intervention... - Local not systemic modulation of dendritic cell S1P receptors in lung blunts virus-specific immune responses to influenzaDavid Marsolais
Departments of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
Mol Pharmacol 74:896-903. 2008..Thus, our results suggest that locally delivered sphingosine analogs induce immunosuppression by modulating S1P receptors other than S1P(1) or S1P(2) on dendritic cells in the lungs after influenza virus infection... - Endothelial cells are central orchestrators of cytokine amplification during influenza virus infectionJohn R Teijaro
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
Cell 146:980-91. 2011..Modulation of endothelium with a specific agonist suggests that diseases in which amplification of cytokine storm is a significant pathological component could be chemically tractable... - Treatment with a sphingosine analog does not alter the outcome of a persistent virus infectionKevin B Walsh
Department of Immunology and Microbial Science, The Scripps Research Institute, IMM 6, TSRI, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Virology 397:260-9. 2010..Therefore, treatment with a sphingosine analog does not ameliorate persistent LCMV-Cl 13 infection... - CD69 down-modulation and inhibition of thymic egress by short- and long-term selective chemical agonism of sphingosine 1-phosphate receptorsChristopher Alfonso
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Eur J Immunol 36:149-59. 2006.... - A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infectionDavid Marsolais
Department of Chemical Physiology and Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 106:1560-5. 2009..These data indicate that sphingosine analogs display useful potential for controlling the immunopathology caused by influenza virus... - Essential requirement for sphingosine kinase 2 in a sphingolipid apoptosis pathway activated by FTY720 analoguesAnthony S Don
Departments of Immunology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 282:15833-42. 2007.... - Ligand-binding pocket shape differences between sphingosine 1-phosphate (S1P) receptors S1P1 and S1P3 determine efficiency of chemical probe identification by ultrahigh-throughput screeningSTEPHAN C SCHURER
Department of Scientific Computing, The Scripps Research Institute, La Jolla, California and Jupiter, Florida, USA
ACS Chem Biol 3:486-98. 2008.... - Actions of a picomolar short-acting S1P₁ agonist in S1P₁-eGFP knock-in miceStuart M Cahalan
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
Nat Chem Biol 7:254-6. 2011..We demonstrate differential downregulation of S1P(1) on lymphocytes and endothelia after agonist treatment... - Potent and selective inhibitors of glutathione S-transferase omega 1 that impair cancer drug resistanceKatsunori Tsuboi
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 133:16605-16. 2011..Cancer cells treated with KT53 show heightened sensitivity to the cytotoxic effects of cisplatin, supporting a role for GSTO1 in chemotherapy resistance... - SAR analysis of innovative selective small molecule antagonists of sphingosine-1-phosphate 4 (S1P₄) receptorMariangela Urbano
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, United States
Bioorg Med Chem Lett 21:5470-4. 2011..By expanding the molecular diversity within the hit-derived class, our SAR study provides innovative small molecule potent and selective S1P(4) antagonists suitable for in vivo pharmacological validation of the target receptor... - Mapping pathways downstream of sphingosine 1-phosphate subtype 1 by differential chemical perturbation and proteomicsPedro J Gonzalez Cabrera
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 282:7254-64. 2007..These data suggest that the hierarchy of ubiquitin recruitment to S1P(1) (AFD-R > S1P > SEW2871) correlates with the efficiency of lysosomal receptor degradation and reflects intrinsic differences between agonists... - Confirming target engagement for reversible inhibitors in vivo by kinetically tuned activity-based probesAlexander Adibekian
Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 134:10345-8. 2012.... - Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rateM Germana Sanna
Department of Immunology, The Center for Mass Spectrometry, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 279:13839-48. 2004.... - S1P1-selective in vivo-active agonists from high-throughput screening: off-the-shelf chemical probes of receptor interactions, signaling, and fateEuijung Jo
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, ICND 118, La Jolla, CA 92037, USA
Chem Biol 12:703-15. 2005.... - Design, synthesis and SAR analysis of novel potent and selective small molecule antagonists of NPBWR1 (GPR7)Mariangela Urbano
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 22:7135-41. 2012..This lead molecule may provide a pharmacological tool to clarify the molecular basis of the in vivo physiological function and therapeutic utility of NPBWR1 in diverse disease areas including inflammatory pain and eating disorders... - Dissecting influenza virus pathogenesis uncovers a novel chemical approach to combat the infectionMichael B A Oldstone
Viral Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
Virology 435:92-101. 2013..The functional mechanism of S1P receptor agonist(s) action and the predominant role played by pulmonary endothelial cells as amplifiers of cytokine storm during influenza infection are described... - Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1Daniel A Bachovchin
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Med Chem 54:5229-36. 2011.... - Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3-alkyl-2-(alkylimino)thiazolidin-4-one chemotypeMariangela Urbano
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 21:6739-45. 2011..The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the effects of the S1P(4)-R signaling cascade and elucidate the molecular basis of the receptor function... - Real-time differential labeling of blood, interstitium, and lymphatic and single-field analysis of vasculature dynamics in vivoGor Sarkisyan
Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Rd MEM L55, La Jolla, CA 92037, USA
Am J Physiol Cell Physiol 302:C1460-8. 2012..Last, single-field fluid movement dynamics can be derived, allowing for the simultaneous determination of fluid flow rates in diverse blood and lymphatic compartments... - Quelling the storm: utilization of sphingosine-1-phosphate receptor signaling to ameliorate influenza virus-induced cytokine stormKevin B Walsh
Department of Immunology and Microbial Science, The Scripps Research Institute, IMM 6, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA
Immunol Res 51:15-25. 2011.... - S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNFYasuhiro Gon
Department of Immunology, Core Microscopy Facility, Helen L Dorris Child and Adolescent Neuro Psychiatric Disorder Institute, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 102:9270-5. 2005..Because S1P3-null mice are resistant to S1P-induced pulmonary leakage, either alone or in the presence of TNF, S1P3 antagonism may be useful in protecting epithelial integrity in pulmonary disease... - Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitorsDaniel A Bachovchin
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 108:6811-6. 2011.... - Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virusKevin B Walsh
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 108:12018-23. 2011..With cytokine storm playing a role in the pathogenesis of a wide assortment of viral, bacterial, and immunologic diseases, a therapeutic approach using sphingosine analogs is of particular interest... - Discovery, design and synthesis of the first reported potent and selective sphingosine-1-phosphate 4 (S1P4) receptor antagonistsMiguel Guerrero
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States
Bioorg Med Chem Lett 21:3632-6. 2011.... - SAR analysis of novel non-peptidic NPBWR1 (GPR7) antagonistsMiguel Guerrero
Department of Chemistry, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Bioorg Med Chem Lett 23:614-9. 2013.... - Selective inhibitors and tailored activity probes for lipoprotein-associated phospholipase A(2)Joseph M G Nagano
The Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Rd La Jolla, CA 92037, United States The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N Torrey Pines Rd La Jolla, CA 92037, United States
Bioorg Med Chem Lett 23:839-43. 2013..Our findings thus identify both inhibitors and chemoproteomic probes that are suitable for investigating Lp-PLA(2) function in biological systems... - Novel selective allosteric and bitopic ligands for the S1P(3) receptorEuijung Jo
Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
ACS Chem Biol 7:1975-83. 2012.... - Oxime esters as selective, covalent inhibitors of the serine hydrolase retinoblastoma-binding protein 9 (RBBP9)Daniel A Bachovchin
Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Rd La Jolla, CA 92037, United States
Bioorg Med Chem Lett 20:2254-8. 2010.... - Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammationFrank Niessen
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
Nature 452:654-8. 2008..Thus, activation of dendritic cells by coagulation in the lymphatics emerges as a previously unknown mechanism that promotes systemic inflammation and lethality in decompensated innate immune responses... - The function of follicular helper T cells is regulated by the strength of T cell antigen receptor bindingNicolas Fazilleau
Department of Immunology and Microbial Sciences, La Jolla, California, USA
Nat Immunol 10:375-84. 2009..Our studies demonstrate a central function for differences in the binding strength of the T cell antigen receptor in the antigen-specific mechanisms that 'program' specialized effector T(FH) function in vivo... - CD8+ T cell tolerance in nonobese diabetic mice is restored by insulin-dependent diabetes resistance allelesXavier Martinez
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
J Immunol 175:1677-85. 2005..These results underscore the variety of ways that autoimmunity can be prevented and identify the elimination of islet-specific CD8+ T cells as a common indicator of high-level protection... - Modulation of chemokines and allergic airway inflammation by selective local sphingosine-1-phosphate receptor 1 agonism in lungsDavid Marsolais
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA
Mol Pharmacol 79:61-8. 2011..Specific S1P₁ agonism in lungs contributes significantly to anti-inflammatory activities of sphingosine-1-phosphate therapeutics by suppressing chemokine release in the airways, and may be of clinical relevance... - Chemical modulators of sphingosine-1-phosphate receptors as barrier-oriented therapeutic moleculesDavid Marsolais
Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Nat Rev Drug Discov 8:297-307. 2009..This Review discusses the role of sphingosine-1-phosphate receptors in the regulation and protection of biological barriers, and the potential of therapeutic strategies that target this receptor family... - S1P1-selective agonist SEW2871 exacerbates reperfusion arrhythmiasYayoi T Tsukada
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
J Cardiovasc Pharmacol 50:660-9. 2007..This is the first demonstration of the critical role of the S1P1 receptor in I/R injury... - Lysophospholipid receptors as potential drug targets in tissue transplantation and autoimmune diseasesJerold Chun
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Curr Pharm Des 12:161-71. 2006..Here we provide a brief introduction to receptor-mediated lysophospholipid signaling and discuss its basic and potential therapeutic roles in autoimmune-related diseases... - Novel inhibitors for PRMT1 discovered by high-throughput screening using activity-based fluorescence polarizationMyles B C Dillon
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, United States
ACS Chem Biol 7:1198-204. 2012.... - High-throughput screening for inhibitors of sialyl- and fucosyltransferasesCory D Rillahan
Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
Angew Chem Int Ed Engl 50:12534-7. 2011..The screening of 16,000 compounds against different glycosyltransferases has identified various interesting inhibitors... - Sphingosine 1-phosphate and its receptors: an autocrine and paracrine networkHugh Rosen
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Nat Rev Immunol 5:560-70. 2005..S1P-S1P-receptor regulatory systems might therefore be novel targets for the therapy of diverse immunological diseases... - Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case studyRyuichiro Nakai
Department of Chemical Physiology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Bioorg Med Chem 17:1101-8. 2009..We anticipate that ABPP will find general utility as a platform to rank the selectivity of lead compounds emerging from HTS assays for a wide variety of enzymes... - Application of beta-lactamase enzyme complementation to the high-throughput screening of toll-like receptor signaling inhibitorsHyun Ku Lee
Department of Immunology, IMM 12, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mol Pharmacol 72:868-75. 2007..7 cells. One compound is effective near 100 nM. None of the compounds showed any cytotoxicity at 20 microM... - A fluorescent plate reader assay for ceramide kinaseAnthony S Don
Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA 92037, USA
Anal Biochem 375:265-71. 2008.... - A GTP affinity probe for proteomics highlights flexibility in purine nucleotide selectivityElizabeth A George Cisar
The Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
J Am Chem Soc 135:4676-9. 2013..The GTP-BP-yne probe will be a useful tool for the study of GTP-binding proteins, especially when targets of interest are not known a priori... - A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cellsDavide Gianni
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA
ACS Chem Biol 5:981-93. 2010..These results elucidate the relevance of Nox1-dependent ROS generation in mechanisms of cancer invasion and define ML171 as a useful Nox1 chemical probe and potential therapeutic agent for inhibition of cancer cell invasion... - Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probesDaniel A Bachovchin
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA
Nat Biotechnol 27:387-94. 2009..Furthermore, we show that the detoxification enzyme GSTO1, also implicated in cancer, is inhibited by several electrophilic compounds found in public libraries, some of which display high selectivity for this protein... - Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonistsSuzanne Mandala
Department of Immunology and Rheumatology, Merck Research Laboratories, Post Office Box 2000, Rahway, NJ 07065, USA
Science 296:346-9. 2002..Inhibition of lymphocyte recirculation by activation of S1P receptors may result in therapeutically useful immunosuppression... - Sphingosine-1-phosphate receptor agonism impairs the efficiency of the local immune response by altering trafficking of naive and antigen-activated CD4+ T cellsJenny H Xie
Department of Pharmacology, Merck Research Laboratories, Rahway NJ 07065, USA
J Immunol 170:3662-70. 2003..Thus, FTY720 induces immunosuppression through inhibition of both the recirculation of naive T cells and the release of Ag-activated T cells from the DLN to lymph and to the blood compartment... - The discovery of 3-(N-alkyl)aminopropylphosphonic acids as potent S1P receptor agonistsJeffrey J Hale
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 14:3495-9. 2004..3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes... - Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonistsJeffrey J Hale
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 14:3501-5. 2004.... - Potent S1P receptor agonists replicate the pharmacologic actions of the novel immune modulator FTY720Jeffrey J Hale
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 14:3351-5. 2004..The similar S1P receptor profiles of 2 and 19 coupled with their comparable potency in vivo supports a connection between S1P receptor agonism and immunosuppressive efficacy... - Regulation of immunity by lysosphingolipids and their G protein-coupled receptorsEdward J Goetzl
Department of Medicine, UCSF, San Francisco, California, USA
J Clin Invest 114:1531-7. 2004.... - Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinusesSindy H Wei
Department of Physiology and Biophysics and Center for Immunology, University of California, Irvine, California 92697 4561, USA
Nat Immunol 6:1228-35. 2005..Our results provide visualization of transendothelial migration of T cells into lymphatic sinuses and suggest that S1P(1) agonists act mainly on endothelial cell S1P(1) receptors to inhibit lymphocyte migration... - A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonistsJeffrey J Hale
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA
J Med Chem 47:6662-5. 2004..Analogues 18 and 24 are highly orally bioavailable and possess excellent pharmacokinetic profiles in the rat, dog, and rhesus monkey... - Design and synthesis of conformationally constrained 3-(N-alkylamino)propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptorsLin Yan
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA
Bioorg Med Chem Lett 14:4861-6. 2004.... - A fully automated [35S]GTPgammaS scintillation proximity assay for the high-throughput screening of Gi-linked G protein-coupled receptorsMarc Ferrer
Department of Automated Biotechnology, Merck Research Laboratories, North Wales, Pennsylvania, USA
Assay Drug Dev Technol 1:261-73. 2003..Here we compare [(35)S]GTPgammaS scintillation proximity binding assays for two different G(i)-coupled GPCRs, and describe their implementation with automated high-throughput systems... - Molecular characterization of the murine SIGNR1 gene encoding a C-type lectin homologous to human DC-SIGN and DC-SIGNRStephen A Parent
Department of Immunology and Rheumatology, Merck Research Laboratories, PO Box 2000, RY 80Y 225, Rahway, NJ 07065, USA
Gene 293:33-46. 2002..In situ hybridization and immunocytochemistry experiments demonstrate that, like human DC-SIGN, the murine messenger RNAs are expressed in subsets of dendritic cells in the spleen and skin... - Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3Zhen Li
Department of Medicinal Chemistry, Merck Research Laboratory, Rahway, New Jersey 07065, USA
J Med Chem 48:6169-73. 2005..Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy...
Research Grants
- S1P Receptor subtypes: Regulating lymphocyte traffickingHugh Rosen; Fiscal Year: 2007..These studies will yield an enhanced understanding of the basic mechanisms by which S1P receptor agonism induces clinically useful immunosuppression of potential use in autoimmunity. ..
- Molecular Libraries Screening Centers Network (MLSCN)(RMI)Hugh Rosen; Fiscal Year: 2007....