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/jm051219xDOI Listing

Publication Analysis

Top Keywords

cck2 antagonists
12
14-benzodiazepine-based cck2
8
cck1 receptors
8
novel achiral
4
achiral 134-benzotriazepine
4
134-benzotriazepine analogues
4
analogues 14-benzodiazepine-based
4
cck2
4
antagonists display
4
display high
4

Similar Publications

Development and Validation of Novel Z-360-Based Macromolecules for the Active Targeting of CCK2-R.

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 PDF

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 PDF
Article Synopsis
  • Micro-environmental factors like stromal and immune cells, along with hormones, significantly influence the progression of melanoma.
  • A study with 89 melanoma patients revealed a notable link between elevated gastrin levels and increased melanoma thickness and metastasis, suggesting higher cancer progression risks.
  • Gastrin was shown to promote melanoma cell migration and invasion through CCK2 receptors, with interactions in the tumor environment potentially exacerbating these effects, especially when combined with dermal fibroblasts/myofibroblasts.
View Article and Find Full Text PDF

Effect of cholecystokinin on small intestinal motility in suncus murinus.

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 PDF

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 PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!