2. Academic Validation
  3. Identification of 2-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)tricyclo[3.3.1.13,7]decane-2-carboxylic Acid (NTRC-844) as a Selective Antagonist for the Rat Neurotensin Receptor Type 2

Identification of 2-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)tricyclo[3.3.1.13,7]decane-2-carboxylic Acid (NTRC-844) as a Selective Antagonist for the Rat Neurotensin Receptor Type 2

  • ACS Chem Neurosci. 2016 Sep 21;7(9):1225-31. doi: 10.1021/acschemneuro.6b00097.
James B Thomas 1,  Mélanie Vivancos 2,  Angela M Giddings 1,  Robert W Wiethe 1,  Keith R Warner 1,  Alexandre Murza 2,  Élie Besserer-Offroy 2,  Jean-Michel Longpré 2,  Scott P Runyon 1,  Ann M Decker 1,  Brian P Gilmour 1,  Philippe Sarret 2
Affiliations

Affiliations

  • 1 Center for Drug Discovery, RTI International , P.O. Box 12194, Research Triangle Park, North Carolina 27709, United States.
  • 2 Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke , 3001, 12th Ave. North, Sherbrooke, QC J1H 5N4, Canada.
PMID: 27359371 DOI: 10.1021/acschemneuro.6b00097
Abstract

Neurotensin Receptor type 2 (NTS2) compounds display analgesic activity in animal pain models. We have identified the first high-affinity NTS2-selective antagonist (8) that is active in vivo. This study also revealed that the NTS2 FLIPR assay designation for a compound, agonist, partial agonist, and so forth, did not correlate with its in vivo activity as observed in the thermal tail-flick acute model of pain. This suggests that calcium mobilization is not the signaling pathway involved in NTS2-mediated analgesia as assessed by the thermal tail-flick model. Finally, we found a significant bias between rat and human for compound 9 in the NTS2 binding assay.

Keywords

FLIPR assay; NT79; NTRC-844; NTS2 receptor; Neurotensin; analgesia; thermal tail-flick.

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