Narender R Gavva

Summary

Affiliation: Amgen Inc
Country: USA

Publications

  1. ncbi request reprint Molecular determinants of vanilloid sensitivity in TRPV1
    Narender 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
  2. doi request reprint 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 rats
    Sonya G Lehto
    Department of Neuroscience, One Amgen Center Dr, Thousand Oaks, CA 91320 1799, USA
    J Pharmacol Exp Ther 326:218-29. 2008
  3. pmc Transient receptor potential melastatin 8 (TRPM8) channels are involved in body temperature regulation
    Narender R Gavva
    Department of Neuroscience, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
    Mol Pain 8:36. 2012
  4. doi request reprint Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1
    Narender R Gavva
    Department of Neuroscience, Amgen, One Amgen Center Drive, Thousand Oaks, CA 91320 1799, USA
    Trends Pharmacol Sci 29:550-7. 2008
  5. doi request reprint Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans
    Narender 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
  6. ncbi request reprint Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade
    Narender 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
  7. ncbi request reprint The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation
    Narender R Gavva
    Department of Neuroscience, Amgen, Thousand Oaks, California 91320 1799, USA
    J Neurosci 27:3366-74. 2007
  8. ncbi request reprint Proton activation does not alter antagonist interaction with the capsaicin-binding pocket of TRPV1
    Narender 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
  9. ncbi request reprint Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic properties
    Hui 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
  10. ncbi request reprint Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidate
    Elizabeth 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

Collaborators

Detail Information

Publications27

  1. ncbi request reprint Molecular determinants of vanilloid sensitivity in TRPV1
    Narender 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...
  2. doi request reprint 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 rats
    Sonya 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...
  3. pmc Transient receptor potential melastatin 8 (TRPM8) channels are involved in body temperature regulation
    Narender 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...
  4. doi request reprint Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1
    Narender 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...
  5. doi request reprint Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans
    Narender 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
    ....
  6. ncbi request reprint Repeated administration of vanilloid receptor TRPV1 antagonists attenuates hyperthermia elicited by TRPV1 blockade
    Narender 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...
  7. ncbi request reprint The vanilloid receptor TRPV1 is tonically activated in vivo and involved in body temperature regulation
    Narender 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...
  8. ncbi request reprint Proton activation does not alter antagonist interaction with the capsaicin-binding pocket of TRPV1
    Narender 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...
  9. ncbi request reprint Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic properties
    Hui 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...
  10. ncbi request reprint Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidate
    Elizabeth 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...
  11. doi request reprint Design and synthesis of peripherally restricted transient receptor potential vanilloid 1 (TRPV1) antagonists
    Nuria 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...
  12. doi request reprint Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonists
    Nuria 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)...
  13. ncbi request reprint Novel vanilloid receptor-1 antagonists: 1. Conformationally restricted analogues of trans-cinnamides
    Mark 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
    ....
  14. ncbi request reprint 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 properties
    Narender 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...
  15. pmc Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists
    Lana 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...
  16. ncbi request reprint Trisubstituted pyrimidines as transient receptor potential vanilloid 1 (TRPV1) antagonists with improved solubility
    Xianghong 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...
  17. doi request reprint 4-Aminopyrimidine tetrahydronaphthols: a series of novel vanilloid receptor-1 antagonists with improved solubility properties
    Elizabeth 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...
  18. ncbi request reprint Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H-benzimidazoles
    Vassil 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)...
  19. doi request reprint Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists
    Markian 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...
  20. ncbi request reprint Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonists
    Vijay 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...
  21. ncbi request reprint A polyclonal antibody to the prepore loop of transient receptor potential vanilloid type 1 blocks channel activation
    Lana Klionsky
    Department of Neuroscience, Amgen Inc, MS 29 2 B, Thousand Oaks, CA 91320 1799, USA
    J Pharmacol Exp Ther 319:192-8. 2006
    ....
  22. ncbi request reprint The TRPV1 receptor and nociception
    David 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...
  23. ncbi request reprint Synthesis and evaluation of thiazole carboxamides as vanilloid receptor 1 (TRPV1) antagonists
    Ning 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...
  24. pmc Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature
    M 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...
  25. doi request reprint Effect of AMG0347, a transient receptor potential type V1 receptor antagonist, and morphine on pain behavior after plantar incision
    Chaoran 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...
  26. ncbi request reprint Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors
    Alexandre 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)...
  27. pmc The vanilloid receptor TRPV1 is activated and sensitized by local anesthetics in rodent sensory neurons
    Andreas 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...