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

Autor: Pearce LV; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH , Bethesda, Maryland 20892-4255, United States., Ann J; Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 08826, Republic of Korea., Jung A; Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 08826, Republic of Korea., Thorat SA; Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 08826, Republic of Korea., Herold BKA; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH , Bethesda, Maryland 20892-4255, United States., Habtemichael AD; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH , Bethesda, Maryland 20892-4255, United States., Blumberg PM; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH , Bethesda, Maryland 20892-4255, United States., Lee J; Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul 08826, Republic of Korea.
Jazyk: angličtina
Zdroj: Journal of medicinal chemistry [J Med Chem] 2017 Oct 12; Vol. 60 (19), pp. 8246-8252. Date of Electronic Publication: 2017 Sep 21.
DOI: 10.1021/acs.jmedchem.7b00859
Abstrakt: 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-[ 3 H])piperidin-1-yl-4-[ 3 H])-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)urea ([ 3 H]MPOU), that embodies improved absolute affinity for human TRPV1 and improved synthetic accessibility.
Databáze: MEDLINE
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