scholarly journals Identification of Novel Endogenous Cytochrome P450 Arachidonate Metabolites with High Affinity for Cannabinoid Receptors

2008 ◽  
Vol 283 (36) ◽  
pp. 24514-24524 ◽  
Author(s):  
Jian-Kang Chen ◽  
Jianchun Chen ◽  
John D. Imig ◽  
Shouzuo Wei ◽  
David L. Hachey ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cannabinoid Receptors ◽  
High Affinity ◽  
Arachidonate Metabolites

Sulfaphenazole Derivatives as Tools for Comparing Cytochrome P450 2C5 and Human Cytochromes P450 2Cs:  Identification of a New High Affinity Substrate Common to Those Enzymes†

Biochemistry ◽  
2003 ◽  
Vol 42 (21) ◽  
pp. 6363-6369 ◽  
Author(s):  
Cristina Marques-Soares ◽  
Sylvie Dijols ◽  
Anne-Christine Macherey ◽  
Michael R. Wester ◽  
Eric F. Johnson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochromes P450 ◽  
High Affinity

scholarly journals The screening of the inhibitors of the human cytochrome P450(51) (CYP51A1): the plant and animal structural lanosterol's analogs

2014 ◽  
Vol 60 (5) ◽  
pp. 528-537 ◽  
Author(s):  
L.A. Kaluzhskiy ◽  
O.V. Gnedenko ◽  
A.A. Gilep ◽  
N.V. Strushkevich ◽  
T.V. Shkel ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Surface Plasmon Resonance ◽  
Active Site ◽  
Cholesterol Biosynthesis ◽  
High Affinity ◽  
Human Cytochrome ◽  
Low Weight ◽  
Biosynthesis Regulation ◽  
Spectral Titration ◽  
Specific Inhibitors

The cholesterol biosynthesis regulation is the important part of the hypercholesterolemia diseases therapy. The inhibition of the post-squalene cholesterol biosynthesis steps provide the alternative to classic statin therapy. Sterol-14a-demethylase (CYP51) is one of the hypothetical targets for it. In this work the screening of the ability to interact with human CYP51 (CYP51A1) for the nature low-weight compounds with steroid-like scaffold were performed by integration of the surface plasmon resonance biosensor and spectral titration methods. The results of the selection were 4 compounds (betulafolientriol, holothurin A, teasaponin, capsicoside A) witch had high affinity to the CYP51A1 active site. These data extend the range of compounds which may be used as specific inhibitors of CYP51 and give the permission to suggest the dynamic of the enzyme.

Novel arachidonate metabolites generated by cytochrome P450-dependent mono-oxygenases

1991 ◽  
Vol 23 (4) ◽  
pp. 309-318 ◽  
Author(s):  
M.A. Carroll ◽  
C.P. Quilley ◽  
J.C. McGiff
Keyword(s):  
Cytochrome P450 ◽  
Arachidonate Metabolites

The contribution of cytochrome P450-dependent arachidonate metabolites to integrated renal function

Steroids ◽  
1993 ◽  
Vol 58 (12) ◽  
pp. 573-579 ◽  
Author(s):  
John C. McGiff ◽  
Caroline P. Quilley ◽  
Mairead A. Carroll
Keyword(s):  
Renal Function ◽  
Cytochrome P450 ◽  
Arachidonate Metabolites

scholarly journals Discovery of High-Affinity Cannabinoid Receptors Ligands through a 3D-QSAR Ushered by Scaffold-Hopping Analysis

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2183 ◽  
Author(s):  
Giuseppe Floresta ◽  
Orapan Apirakkan ◽  
Antonio Rescifina ◽  
Vincenzo Abbate
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
3D Qsar ◽  
Scaffold Hopping ◽  
Design And Optimization ◽  
High Affinity ◽  
Qsar Models ◽  
Visual Understanding ◽  
The Individual ◽  
New Compounds

Two 3D quantitative structure–activity relationships (3D-QSAR) models for predicting Cannabinoid receptor 1 and 2 (CB1 and CB2) ligands have been produced by way of creating a practical tool for the drug-design and optimization of CB1 and CB2 ligands. A set of 312 molecules have been used to build the model for the CB1 receptor, and a set of 187 molecules for the CB2 receptor. All of the molecules were recovered from the literature among those possessing measured Ki values, and Forge was used as software. The present model shows high and robust predictive potential, confirmed by the quality of the statistical analysis, and an adequate descriptive capability. A visual understanding of the hydrophobic, electrostatic, and shaping features highlighting the principal interactions for the CB1 and CB2 ligands was achieved with the construction of 3D maps. The predictive capabilities of the model were then used for a scaffold-hopping study of two selected compounds, with the generation of a library of new compounds with high affinity for the two receptors. Herein, we report two new 3D-QSAR models that comprehend a large number of chemically different CB1 and CB2 ligands and well account for the individual ligand affinities. These features will facilitate the recognition of new potent and selective molecules for CB1 and CB2 receptors.

scholarly journals A Combined Experimental and Simulation Approach to Develop Selective High-Affinity Small-Molecule Inhibitors of Cannabinoid Receptors CB1/CB2

2011 ◽  
Vol 100 (3) ◽  
pp. 548a-549a
Author(s):  
Irene Meliciani ◽  
Nicole Volz ◽  
Viktor Rempel ◽  
Sonja Hinz ◽  
Tadeusz Karcz ◽  
...  
Keyword(s):  
Small Molecule ◽  
Cannabinoid Receptors ◽  
Small Molecule Inhibitors ◽  
Simulation Approach ◽  
High Affinity

scholarly journals Identification of a Heme-sensing Domain in Iron Regulatory Protein 2

2004 ◽  
Vol 279 (44) ◽  
pp. 45450-45454 ◽  
Author(s):  
Jinsook Jeong ◽  
Tracey A. Rouault ◽  
Rodney L. Levine
Keyword(s):  
Cytochrome P450 ◽  
Iron Deficiency ◽  
Iron Metabolism ◽  
Regulatory Protein ◽  
Protein Molecule ◽  
Covalent Modification ◽  
Iron Regulatory Protein ◽  
Cellular Regulation ◽  
High Affinity ◽  
Iron Responsive Elements

Iron regulatory protein 2 coordinates the cellular regulation of iron metabolism by binding to iron-responsive elements in mRNA. The protein is synthesized constitutively but is rapidly degraded when iron stores are replete. The mechanisms that prevent degradation during iron deficiency or promote degradation during iron sufficiency are not delineated. Iron regulatory protein 2 contains a domain not present in the closely related iron regulatory protein 1, and we found that this domain binds heme with high affinity. A cysteine within the domain is axially liganded to the heme, as occurs in cytochrome P450. The protein-bound heme reacts with molecular oxygen to mediate the oxidation of cysteine, including β-elimination of the sulfur to yield alanine. This covalent modification may thus mark the protein molecule for degradation by the proteasome system, providing another mechanism by which heme can regulate the level of iron regulatory protein 2.

scholarly journals Bidirectional regulation of renal cortical Na+,K+-ATPase by protein kinase C.

2004 ◽  
Vol 51 (3) ◽  
pp. 757-772 ◽  
Author(s):  
Jerzy Bełtowski ◽  
Andrzej Marciniak ◽  
Anna Jamroz-Wiśniewska ◽  
Ewelina Borkowska ◽  
Grazyna Wójcicka
Keyword(s):  
Cytochrome P450 ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Atpase Activity ◽  
Inhibitory Effect ◽  
Kinase C ◽  
Bidirectional Regulation ◽  
Male Wistar Rats ◽  
Arachidonate Metabolites ◽  
High Doses

We examined the role of protein kinase C (PKC) in the regulation of Na+,K+- ATPase activity in the renal cortex. Male Wistar rats were anaesthetized and the investigated reagents were infused into the abdominal aorta proximally to the renal arteries. A PKC-activating phorbol ester, phorbol 12,13-dibutyrate (PDBu), had a dose-dependent effect on cortical Na+,K+-ATPase activity. Low dose of PDBu (10(-11) mol/kg per min) increased cortical Na+,K+-ATPase activity by 34.2%, whereas high doses (10(-9) and 10(-8) mol/kg per min) reduced this activity by 22.7% and 35.0%, respectively. PDBu administration caused changes in Na+,K+-ATPase Vmax without affecting K(0.5) for Na+, K+ and ATP as well as Ki for ouabain. The effects of PDBu were abolished by PKC inhibitors, staurosporine, GF109203X, and Gö 6976. The inhibitory effect of PDBu was reversed by pretreatment with inhibitors of cytochrome P450-dependent arachidonate metabolism, ethoxyresorufin and 17-octadecynoic acid, inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin and LY294002, and by actin depolymerizing agents, cytochalasin D and latrunculin B. These results suggest that PKC may either stimulate or inhibit renal cortical Na+,K+-ATPase. The inhibitory effect is mediated by cytochrome P450-dependent arachidonate metabolites and PI3K, and is caused by redistribution of the sodium pump from the plasma membrane to the inactive intracellular pool.

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