Research Topics
Genomes and Genes | Narender R GavvaSummaryAffiliation: Amgen Inc Country: USA Publications
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Publications
Molecular determinants of vanilloid sensitivity in TRPV1Narender R Gavva
Department of Neuroscience, Amgen Inc, MS 29 2 B, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
J Biol Chem 279:20283-95. 2004..Based on our data we propose a model of the TM3/4 region of TRPV1 bound to capsaicin or RTX that may aid in the development of potent TRPV1 antagonists with utility in the treatment of sensory disorders...
Antihyperalgesic effects of (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in ratsSonya G Lehto
Department of Neuroscience, One Amgen Center Dr, Thousand Oaks, CA 91320 1799, USA
J Pharmacol Exp Ther 326:218-29. 2008..Based on the data shown here, we conclude that it is feasible to modulate TRPV1 in a manner that does not cause hyperthermia while maintaining efficacy in rodent pain models...
Transient receptor potential melastatin 8 (TRPM8) channels are involved in body temperature regulationNarender R Gavva
Department of Neuroscience, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Mol Pain 8:36. 2012..Since TRPM8 has been considered as a potential target for chronic pain therapeutics, we have investigated the role of TRPM8 in Tb regulation...- Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1Narender R Gavva
Department of Neuroscience, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
Trends Pharmacol Sci 29:550-7. 2008..However, several other TRPV1 antagonists are currently being evaluated in the clinic and soon-to-be-published results should shed light on the potential of managing antagonist-induced hyperthermia while developing them as therapeutics... - Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humansNarender R Gavva
Department of Neuroscience, MS 29 2 B, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
Pain 136:202-10. 2008.... - Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockadeNarender R Gavva
Department of Neuroscience, MS 29 2 B, One Amgen Center Dr, Thousand Oaks, CA 91320 1799, USA
J Pharmacol Exp Ther 323:128-37. 2007..However, the impact of TRPV1 antagonist-induced hyperthermia on their clinical utility is still unknown... - The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulationNarender R Gavva
Department of Neuroscience, Amgen, Thousand Oaks, California 91320 1799, USA
J Neurosci 27:3366-74. 2007..Together, these results indicate that tonic TRPV1 activation regulates body temperature... - Proton activation does not alter antagonist interaction with the capsaicin-binding pocket of TRPV1Narender R Gavva
Department of Neuroscience, Amgen Inc, MS 29 2 B, One Amgen Center Dr, Thousand Oaks, California 91320 1799, USA
Mol Pharmacol 68:1524-33. 2005..In conclusion, group A antagonists seem to lock the channel conformation in the closed state, blocking both capsaicin and proton activation... - Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic propertiesHui Ling Wang
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, USA
J Med Chem 50:3528-39. 2007..o). Based on its improved overall profile, compound 16p (AMG 628) was selected as a second-generation candidate for further evaluation in human clinical trials as a potential new treatment for chronic pain... - Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidateElizabeth M Doherty
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, USA
J Med Chem 50:3515-27. 2007..o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide; AMG 517) was selected for further evaluation in human clinical trials... - AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic propertiesNarender R Gavva
Department of Neuroscience, Amgen Inc, MS-29-2-B, Thousand Oaks, CA 91320-1799, USA
J Pharmacol Exp Ther 313:474-84. 2005..AMG 9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-induced eye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain... - Design and synthesis of peripherally restricted transient receptor potential vanilloid 1 (TRPV1) antagonistsNuria Tamayo
Chemistry Research and Discovery, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, California 91320, USA
J Med Chem 51:2744-57. 2008..Furthermore, these studies demonstrate that the site of action for TRPV1 blockade elicited hyperthermia is outside the blood-brain barrier... - Novel vanilloid receptor-1 antagonists: 1. Conformationally restricted analogues of trans-cinnamidesMark H Norman
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, USA
J Med Chem 50:3497-514. 2007.... - Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonistsLana Klionsky
Department of Neuroscience, Amgen, Inc, Thousand Oaks, California, USA
Mol Pain 3:39. 2007..In summary, we conclude that both human and rat TRPA1 channels show similar AITC and noxious cold activation profiles, but TCEB compounds display species-specific differential pharmacology at TRPA1... - Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonistsNuria A Tamayo
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, United States
J Med Chem 55:1593-611. 2012..Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS)... - Trisubstituted pyrimidines as transient receptor potential vanilloid 1 (TRPV1) antagonists with improved solubilityXianghong Wang
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
Bioorg Med Chem Lett 17:6539-45. 2007..In addition, compound 26 was found to be orally bioavailable (rat F(oral)=24%) and had potent TRPV1 antagonist activity (capsaicin IC(50)=1.5nM) comparable to that of 1... - 4-Aminopyrimidine tetrahydronaphthols: a series of novel vanilloid receptor-1 antagonists with improved solubility propertiesElizabeth M Doherty
Department of Chemistry Research and Discovery, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
Bioorg Med Chem Lett 18:1830-4. 2008..Synthesis, SAR, and improvements in metabolic stability and absorption of these compounds are described herein... - Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H-benzimidazolesVassil I Ognyanov
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320 1799, USA
J Med Chem 49:3719-42. 2006..Compound 46ad also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund's adjuvant (CFA)... - Substituted aryl pyrimidines as potent and soluble TRPV1 antagonistsMarkian M Stec
Department of Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
Bioorg Med Chem Lett 18:5118-22. 2008..Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1... - Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonistsVijay K Gore
Chemistry Research and Discovery, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Bioorg Med Chem Lett 17:5825-30. 2007..These studies led to the identification of a highly potent and orally bioavailable TRPV1 antagonist, imidazole 33... - A polyclonal antibody to the prepore loop of transient receptor potential vanilloid type 1 blocks channel activationLana Klionsky
Department of Neuroscience, Amgen Inc, MS-29-2-B, Thousand Oaks, CA 91320-1799, USA
J Pharmacol Exp Ther 319:192-8. 2006.... - The TRPV1 receptor and nociceptionDavid C Immke
Amgen Inc, Department of Neuroscience, Thousand Oaks, CA 91320 1799, USA
Semin Cell Dev Biol 17:582-91. 2006..The current understanding of the physiological role the receptor, as well as the potential therapeutic utility and emerging liabilities of TRPV1 modulators are discussed... - Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonistsNing Xi
Chemistry Research and Discovery, Amgen Inc, One Amgen Center Dr, Thousand Oaks, CA 91320, USA
Bioorg Med Chem Lett 15:5211-7. 2005..The IC(50) values of the most potent antagonists were ca. 0.050microM in these assays... - Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperatureM Camila Almeida
Systemic Inflammation Laboratory FeverLab, Trauma Research, St Joseph s Hospital and Medical Center, Phoenix, Arizona 85013, USA
J Neurosci 32:2086-99. 2012..M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system... - Effect of AMG0347, a transient receptor potential type V1 receptor antagonist, and morphine on pain behavior after plantar incisionChaoran Wu
Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
Anesthesiology 108:1100-8. 2008..Doses of morphine lower than those used in most rodent studies were also examined... - Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectorsAlexandre A Steiner
Systemic Inflammation Laboratory, Trauma Research, St Joseph s Hospital, Phoenix, Arizona 85013, USA
J Neurosci 27:7459-68. 2007..We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on T(b)... - The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neuronsAndreas Leffler
Department of Anesthesiology, Friedrich Alexander University Erlangen Nuremberg, Erlangen, Germany
J Clin Invest 118:763-76. 2008..This effect is sufficient to release CGRP, a key component of neurogenic inflammation, and warrants investigation into the role of TRPV1 and TRPA1 in LA-induced neurotoxicity...