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

James B. Thomas; Scott P. Runyon; Ann Marie Decker; Robert W. Wiethe; Keith R. Warner; Brian P. Gilmour; Angela Mara Giddings; James B. Thomas; Melanie Vivancos; Angela Mara Giddings; Robert W. Wiethe; Keith R. Warner; Alexandre Murza; Elie Besserer-Offroy; Jean-Michel Longpre; Scott P. Runyon; Ann Decker; Brian P. Gilmour; Philippe Sarret

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

Thomas, J. B., Vivancos, M., Giddings, A. M., Wiethe, R. W., Warner, K. R., Murza, A., Besserer-Offroy, E., Longpre, J-M., Runyon, S. P., Decker, A. M., Gilmour, B. P., & Sarret, P. (2016). 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 Chemical Neuroscience, 7(9), 1225-1231. https://doi.org/10.1021/acschemneuro.6b00097

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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.