Deciphering the Potency and Longevity of Hoe 140: A Comprehensive In Vitro Analysis of a Bradykinin Antagonist
In isolated organ preparations, both Hoe 140 and the comparator compound concentration-dependently inhibited BK-induced contractions. However, Hoe 140 showed significantly higher potency in guinea-pig ileum and rat uterus preparations, as well as in guinea-pig isolated pulmonary artery, compared to the other compound. Notably, no inhibitory effects were observed in rabbit aorta contractions induced by Des-Arg9-BK.
Hoe 140 also antagonized BK-induced endothelium-derived relaxing factor (EDRF) release and intracellular calcium increase in cultured bovine endothelial cells, with an IC50 indicating its effectiveness at relatively low concentrations. Furthermore, Hoe 140 completely suppressed BK-induced prostacyclin (PGI2) release from these endothelial cells, while the comparator showed weaker antagonism.
Overall, the results highlight Hoe 140 as an exceptionally potent BK antagonist, being two to three orders of magnitude more potent than the other tested compound. This suggests Hoe 140's potential as a highly effective therapeutic agent for conditions where BK receptor antagonism is beneficial.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.
Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.
By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.
Click on the image below to go directly to the Translational Medicine search interface.
