Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was published. On the basis of this structural information, we designed BAY 58-2667 derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity. Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of 20 with the Ns H-NOX domain revealed that the increased conformational distortion at the C-terminal region of αF helix containing 110-114 residues contributes to the higher activation triggered by 20.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902542 | PMC |
| http://dx.doi.org/10.1021/jm400539d | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders.
Pharmacol Res
August 2023
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China. Electronic address:
Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge.
View Article and Find Full Text PDFMethylene Blue Inhibits Cromakalim-Activated K Currents in Follicle-Enclosed Oocytes.
Membranes (Basel)
January 2023
Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait.
The effects of methylene blue (MB) on cromakalim-induced K currents were investigated in follicle-enclosed oocytes. In concentrations ranging from 3-300 μM, MB inhibited K currents (IC: 22.4 μM) activated by cromakalim, which activates K channels.
View Article and Find Full Text PDFHyperelastic and damage properties of the hypoxic aorta treated with Cinaciguat.
J Biomech
January 2023
Programa de Fisiopatología, Facultad de Medicina, Instituto de Ciencias Biomédicas, Universidad de Chile, Santiago, Chile; International Center for Andean Studies (INCAS), Universidad de Chile, Putre, Chile.
Chronic hypoxia during gestation and postnatal period induces pulmonary hypertension, aorta stiffening and vascular remodeling. In this study, we hypothesized that a postnatal treatment with Cinaciguat, a guanylate cyclase activator, may improve the vascular function by enhancing NO-sGC pathways that induce vasodilation. To assess this, we collected aortas from six lambs gestated, born and raised at 3600 masl.
View Article and Find Full Text PDFInhibition of multidrug resistance proteins by MK571 restored the erectile function in obese mice through cGMP accumulation.
Andrology
March 2023
Department of Translation Medicine (Pharmacology area), Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Background: Intracellular levels of cyclic nucleotides can also be controlled by the action of multidrug resistance protein types 4 (MRP4) and 5 (MRP5). To date, no studies evaluated the role of their inhibition in an animal model of erectile dysfunction (ED).
Objectives: To evaluate the effect of a 2-week treatment with MK571, an inhibitor of the efflux of cyclic nucleotides in the ED of obese mice.
SOLUBLE GUANYLYL CYCLASE ACTIVATION RESCUES HYPEROXIA-INDUCED DYSFUNCTION OF VASCULAR RELAXATION.
Shock
October 2022
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee.
Introduction: Perioperative alterations in perfusion lead to ischemia and reperfusion injury, and supplemental oxygen is administered during surgery to limit hypoxic injury but can lead to hyperoxia. We hypothesized that hyperoxia impairs endothelium-dependent and endothelium-independent vasodilation but not the vasodilatory response to heme-independent soluble guanylyl cyclase activation. Methods: We measured the effect of oxygen on vascular reactivity in mouse aortas.
View Article and Find Full Text PDFWant 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!