A series of 1,3,4-benzotriazepine-based CCK(2) antagonists have been devised by consideration of the structural features that govern CCK receptor affinity and the receptor subtype selectivity of 1,4-benzodiazepine-based CCK(2) antagonists. In contrast to the latter compounds, these novel 1,3,4-benzotriazepines are achiral, yet they display similar affinity for CCK(2) receptors to the earlier molecules and are highly selective over CCK(1) receptors.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1021/jm051219x | DOI Listing |
Mol Pharm
August 2024
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy.
The cholecystokinin type 2 receptor (CCK2-R) represents an ideal target for cancer therapy since it is overexpressed in several tumors and is associated with poor prognosis. Nastorazepide (Z-360), a selective CCK2-R antagonist, has been widely investigated as a CCK2-R ligand for targeted therapy; however, its high hydrophobicity may represent a limit to cell selectivity and optimal in vivo biodistribution. Here, we present three new fluorescent Z-360 derivatives () in which nastorazepide was linked, through spacers bearing different saccharides (glucose (G), lactose (L), and maltotriose (M)), to sulforhodamine B.
View Article and Find Full Text PDFBiomedicines
May 2024
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17036, USA.
The poor prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is due in part to the highly fibrotic nature of the tumors that impedes delivery of therapeutics, including nanoparticles (NPs). Our prior studies demonstrated that proglumide, a cholecystokinin receptor (CCKR) antagonist, reduced fibrosis pervading PanIN lesions in mice. Here, we further detail how the reduced fibrosis elicited by proglumide achieves the normalization of the desmoplastic tumor microenvironment (TME) and improves nanoparticle uptake.
View Article and Find Full Text PDFInt J Mol Sci
November 2023
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 7BE, UK.
Gen Comp Endocrinol
October 2023
Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan; Research Area of Evolutionary Molecular Design, Graduate School of Science and Engineering, Saitama University, 255 Shimo-ohkubo, Sakuraku, Saitama 338-8570, Japan. Electronic address:
In a fasting gastrointestinal tract, a characteristic cyclical rhythmic migrating motor complex (MMC) occur that comprises of three phases: I, II, and III. Among these, phase III contractions propagate from the stomach to the lower intestine in mammals, including humans, dogs, and Suncus murinus (suncus). Apart from the phase III of MMC propagating from the stomach, during the gastric phase II, small intestine-originated strong contractions propagate to the lower small intestine; however, the mechanism of contractions originating in the small intestine has not been clarified.
View Article and Find Full Text PDFJ Neuroendocrinol
November 2023
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
The physiology of gastric acid secretion is one of the earliest subjects in medical literature and has been continuously studied since 1833. Starting with the notion that neural stimulation alone drives acid secretion, progress in understanding the physiology and pathophysiology of this process has led to the development of therapeutic strategies for patients with acid-related diseases. For instance, understanding the physiology of parietal cells led to the developments of histamine 2 receptor blockers, proton pump inhibitors (PPIs), and recently, potassium-competitive acid blockers.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!