MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice - Université Toulouse III - Paul Sabatier - Toulouse INP Accéder directement au contenu
Article Dans Une Revue Molecules Année : 2021

MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice

Magali Jullian
Lukasz Frankiewicz
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Mathieu Galibert
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Thierry Le Diguarher
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Philippe Dupuis
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Amber Ko
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Marc Bertrand
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Anne Pecquery
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Karine Puget
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Résumé

Melanin-concentrating hormone (MCH) is a 19 amino acid long peptide found in the brain of animals, including fishes, batrachians, and mammals. MCH is implicated in appetite and/or energy homeostasis. Antagonists at its receptor (MCH-R1) could be major tools (or ultimately drugs) to understand the mechanism of MCH action and to fight the obesity syndrome that is a worldwide societal health problem. Ever since the deorphanisation of the MCH receptor, we cloned, expressed, and characterized the receptor MCH-R1 and started a vast medicinal chemistry program aiming at the discovery of such usable compounds. In the present final work, we describe GPS18169, a pseudopeptide antagonist at the MCH-R1 receptor with an affinity in the nanomolar range and a Ki for its antagonistic effect in the 20 picomolar range. Its metabolic stability is rather ameliorated compared to its initial parent compound, the antagonist S38151. We tested it in an in vivo experiment using high diet mice. GPS18169 was found to be active in limiting the accumulation of adipose tissues and, correlatively, we observed a normalization of the insulin level in the treated animals, while no change in food or water consumption was observed.
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Dates et versions

hal-03541598 , version 1 (24-01-2022)

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Jean A Boutin, Magali Jullian, Lukasz Frankiewicz, Mathieu Galibert, Philippe Gloanec, et al.. MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice. Molecules, 2021, 26 (5), pp.1291. ⟨10.3390/molecules26051291⟩. ⟨hal-03541598⟩
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