8fgr: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,843 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,332,843 edits
No edit summary
 
Line 10: Line 10:
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.<ref>PMID:17264164</ref>  Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>  
[https://www.uniprot.org/uniprot/NOS3_HUMAN NOS3_HUMAN] Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.<ref>PMID:17264164</ref>  Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.<ref>PMID:17264164</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A series of potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors (hnNOS), based on a difluorobenzene ring linked to a 2-aminopyridine scaffold with different functionalities at the 4-position, is reported. In our efforts to develop novel nNOS inhibitors for the treatment of neurodegenerative diseases, we discovered 17, which showed excellent potency toward both rat (K(i) 15 nM) and human nNOS (K(i) 19 nM), with 1075-fold selectivity over human eNOS and 115-fold selectivity over human iNOS. 17 also showed excellent permeability (P(e) = 13.7 x 10(-6) cm s(-1)), a low efflux ratio (ER 0.48), along with good metabolic stability in mouse and human liver microsomes, with half-lives of 29 and &gt;60 min, respectively. X-ray cocrystal structures of inhibitors bound with three NOS enzymes, namely, rat nNOS, human nNOS, and human eNOS, revealed detailed structure-activity relationships for the observed potency, selectivity, and permeability properties of the inhibitors.
Potent, Selective, and Membrane Permeable 2-Amino-4-Substituted Pyridine-Based Neuronal Nitric Oxide Synthase Inhibitors.,Vasu D, Do HT, Li H, Hardy CD, Awasthi A, Poulos TL, Silverman RB J Med Chem. 2023 Jul 27;66(14):9934-9953. doi: 10.1021/acs.jmedchem.3c00782. Epub , 2023 Jul 11. PMID:37433128<ref>PMID:37433128</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fgr" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Latest revision as of 15:15, 13 August 2026

Structure of human endothelial nitric oxide synthase heme domain in complex with 6-(5-(2-aminoethyl)-2,3-difluorophenethyl)-4-methylpyridin-2-amine

8fgr, resolution 1.98Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=8fgr&oldid=4480717"