A research is presented on quantitative structure-activity relationship (QSAR) studies on the more recent class of non-peptidic CCK(1) receptor antagonists. Our results suggest that the balance of hydrophobicity and volume dependent polarizability term plays a key role in the antagonism of CCK(1) receptor. The size of the substitution of ligands at particular position which induce steric fit is crucial as well as their hydrophobic contribution. Indicator variables were used after the best model was found to account for the usual structural features. The CoMFA results show a good variance explanation and the best self-predictivity is slightly lower than 60% with both leave-one-out and random-group methods. The CoMFA molecular fields showed the importance of steric hindrance of the substituent. From the GRIND models it can be deduced that the shape differences of the molecules are secondary in the regulation of the activity, or better, that their polar substituents are capable of occupying the same zones of the space in the most of the cases.
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Introduction: The developed domestic retrodipeptide analogue of cholecystokinin tetrapeptide (CCK) (N-(6-phenylhexanoyl)-glycyltryptophan amide, or compound GB-115) with antagonistic properties in relation to CCK1 receptors has anxiolytic activity previously shown in preclinical and clinical studies. The aim of the study was to evaluate the anxiolytic effect of GB-115 as a tablet form with subchronic oral administration in comparison with phenazepam in nonhuman primates.
Materials And Methods: The study was conducted on four male rhesus monkeys (Macaca mulatta) aged 5.
Corrigendum to "Spinal CCK1 Receptors Contribute to Somatic Pain Hypersensitivity Induced by Malocclusion Via a Reciprocal Neuron-Glial Signaling Cascade" [J Pain 23 (2022) 1629-1645].
J Pain
November 2024
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Research Center of Stomatology, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK receptors.
Neuropharmacology
November 2024
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Xi'an Jiaotong University College of Stomatology, 98 West 5th Road, Xi'an, Shaanxi, 710004, China; Department of Neural and Pain Sciences, School of Dentistry, The UM Center to Advance Chronic Pain Research, University of Maryland Baltimore, 650 West Baltimore Street, Baltimore, MD, 21201, USA. Electronic address:
Article Synopsis
- * A study on mice exposed to chronic stress revealed that they exhibited anxiety, depression-like behaviors, and long-lasting widespread pain across multiple body regions.
- * The research identified an increase in cholecystokinin (CCK) receptor expression in the spinal cord after stress, suggesting that targeting these receptors could lead to new treatments for chronic primary pain.
Discovery of novel glucagon-like peptide 1/cholecystokinin 1 receptor dual agonists.
Eur J Pharm Sci
August 2024
School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China.
The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. The potential of developing novel dual agonists targeting both cholecystokinin 1 (CCK-1) receptor and glucagon-like peptide 1 (GLP-1) receptor to improve the treatment of type 2 diabetes and obesity have not been fully explored. In this investigation, we reported a series of novel GLP-1/CCK-1 receptor co-agonists constructed by linking the C-terminus of a GLP-1 receptor agonist (bullfrog GLP-1) to the N-terminus of a CCK-1 receptor selective agonist NN9056.
View Article and Find Full Text PDFCholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.
Dig Dis Sci
April 2024
Greater Los Angeles Veterans Affairs Healthcare System, B114, R217, West LA VAMC, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA.
Background/aims: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice.
Methods: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.
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