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Novel Radiolabeled Vanilloid with Enhanced Specificity for Human Transient Receptor Potential Vanilloid 1 (TRPV1).

ABSTRACT: Transient receptor potential vanilloid 1 (TRPV1) has emerged as a promising therapeutic target. While radiolabeled resiniferatoxin (RTX) has provided a powerful tool for characterization of vanilloid binding to TRPV1, TRPV1 shows 20-fold weaker binding to the human TRPV1 than to the rodent TRPV1. We now describe a tritium radiolabeled synthetic vanilloid antagonist, 1-((2-(4-(methyl-[3H])piperidin-1-yl-4-[3H])-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)urea ([3H]MPOU), that embodies improved absolute affinity for human TRPV1 and improved synthetic accessibility.

SUBMITTER: Pearce LV

PROVIDER: S-EPMC6959550 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Novel Radiolabeled Vanilloid with Enhanced Specificity for Human Transient Receptor Potential Vanilloid 1 (TRPV1).

Pearce Larry V LV Ann Jihyae J Jung Aeran A Thorat Shivaji A SA Herold Brienna K A BKA Habtemichael Amelework D AD Blumberg Peter M PM Lee Jeewoo J

Journal of medicinal chemistry 20170921 19

Transient receptor potential vanilloid 1 (TRPV1) has emerged as a promising therapeutic target. While radiolabeled resiniferatoxin (RTX) has provided a powerful tool for characterization of vanilloid binding to TRPV1, TRPV1 shows 20-fold weaker binding to the human TRPV1 than to the rodent TRPV1. We now describe a tritium radiolabeled synthetic vanilloid antagonist, 1-((2-(4-(methyl-[<sup>3</sup>H])piperidin-1-yl-4-[<sup>3</sup>H])-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(3-oxo-3,4-dihydro-2H- ...[more]

PMID: 28892388

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