TY - JOUR
T1 - Compounds Interacting with Cholecystokinin as Potential Drugs Against Excessive Weight Gain and Obesity
AU - Vique-Sánchez, José Luis
AU - López Lujano, Paola Guadalupe
AU - Rodríguez Fonseca, Karla Alejandra
AU - Benítez-Cardoza, Claudia Guadalupe
N1 - Publisher Copyright:
© 2023 Wiley-VCH GmbH.
PY - 2023/4/25
Y1 - 2023/4/25
N2 - Cholecystokinin (CCK) is a peptide family that functions pancreatic enzyme secretion, gallbladder contraction, intestinal motility, satiety, and stomach acid secretion. The CCK peptides are derived from pro-CCK with a specific amino acid sequence (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) at their C-terminus, where the Tyr residue is sulfated. The CCK peptides are ligands of the CCK receptors 1 (CCK1) and 2 (CCK2). In this study, we propose an approach for treating overweight and obese patients, preventing or reducing CCK1 activation using compounds that specifically interact with CCK peptides to regulate their interactions with CCK1. The compounds were selected by molecular docking using a chemical library with the selected residues (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) in CCK. Their effects were evaluated in a diet-induced obese mice model. We show that compounds K2 and K5 decreased and maintained the body weight of the diet-induced obese mice model, respectively, likely by preventing/hindering interactions between CCK peptides and CCK1, modifying its activity. This study demonstrates another approach to treating overweight and obesity by regulating CCK1 functions. The K2 and K5 compounds have properties supporting their continued development as new drugs against these risk factors.
AB - Cholecystokinin (CCK) is a peptide family that functions pancreatic enzyme secretion, gallbladder contraction, intestinal motility, satiety, and stomach acid secretion. The CCK peptides are derived from pro-CCK with a specific amino acid sequence (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) at their C-terminus, where the Tyr residue is sulfated. The CCK peptides are ligands of the CCK receptors 1 (CCK1) and 2 (CCK2). In this study, we propose an approach for treating overweight and obese patients, preventing or reducing CCK1 activation using compounds that specifically interact with CCK peptides to regulate their interactions with CCK1. The compounds were selected by molecular docking using a chemical library with the selected residues (Asp, Tyr, Met, Gly, Trp, Met, Asp, and Phe) in CCK. Their effects were evaluated in a diet-induced obese mice model. We show that compounds K2 and K5 decreased and maintained the body weight of the diet-induced obese mice model, respectively, likely by preventing/hindering interactions between CCK peptides and CCK1, modifying its activity. This study demonstrates another approach to treating overweight and obesity by regulating CCK1 functions. The K2 and K5 compounds have properties supporting their continued development as new drugs against these risk factors.
KW - CCK
KW - Docking
KW - Drug development
KW - Obesity
KW - Overweight
UR - http://www.scopus.com/inward/record.url?scp=85153740573&partnerID=8YFLogxK
U2 - 10.1002/slct.202300196
DO - 10.1002/slct.202300196
M3 - Artículo
AN - SCOPUS:85153740573
SN - 2365-6549
VL - 8
JO - ChemistrySelect
JF - ChemistrySelect
IS - 16
M1 - e202300196
ER -