Jolien De Neve, Khadija Elhabazi, Simon Gonzalez, Claire Herby, Séverine Schneider, Valérie Utard, Rosine Fellmann-Clauss, Nathalie Petit-Demouliere, Sandra Lecat, Mélanie Kremer, Aurelia Ces, François Daubeuf, Charlotte Martin, Steven Ballet, Frédéric Bihel, Frédéric Simonin
The design of bifunctional compounds is a promising approach toward the development of strong analgesics with reduced side effects. We here report the optimization of the previously published lead peptide KGFF09 , which contains opioid receptor agonist and neuropeptide FF receptor antagonist pharmacophores and is shown to induce potent antinociception and reduced side effects. We evaluated the novel hybrid peptides for their in vitro activity at MOP, NPFFR1, and NPFFR2 and selected four of them ( DP08/14/32/50 ) for assessment of their acute antinociceptive activity in mice...
April 30, 2024: Journal of Medicinal Chemistry