دورية أكاديمية
A non-acidic sulfaphenazole analog demonstrating high intrinsic clearance and selectivity by canine CYP2C21.
| العنوان: | A non-acidic sulfaphenazole analog demonstrating high intrinsic clearance and selectivity by canine CYP2C21. |
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| المؤلفون: | Locuson CW; Pfizer Animal Health, Veterinary Medicine Research and Development, Metabolism & Safety, Kalamazoo, MI 49001, USA. charles.w.locuson@pfizer.com, Alfaro JF, Zaya MJ, Billen D, White JA, Jones JP |
| المصدر: | Drug metabolism letters [Drug Metab Lett] 2011 Dec; Vol. 5 (4), pp. 253-8. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101313587 Publication Model: Print Cited Medium: Internet ISSN: 1874-0758 (Electronic) Linking ISSN: 18723128 NLM ISO Abbreviation: Drug Metab Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Saif Zone, Sharjah, U.A.E. : Bentham Science Publishers |
| مواضيع طبية MeSH: | Molecular Probes*, Cytochrome P-450 Enzyme System/*metabolism , Sulfaphenazole/*metabolism, Animals ; Biotransformation ; Chromatography, Liquid ; Dealkylation ; Dogs ; Hydroxylation ; Kinetics ; Metabolic Clearance Rate ; Methylation ; Molecular Structure ; Recombinant Proteins/metabolism ; Substrate Specificity ; Sulfaphenazole/analogs & derivatives ; Sulfaphenazole/chemistry ; Tandem Mass Spectrometry |
| مستخلص: | In contrast to human CYP2C9, non-human CYP2C enzymes do not appear to preferentially bind and metabolize anionic drugs. Using analogs of sulfaphenazole, the effect of an acidic sulfonamide group on apparent affinity and turnover rates was characterized with canine CYP2C21. Blocking the sulfonamide with a methyl group increased the intrinsic clearance by CYP2C21 > 100-fold and decreased K(m). Furthermore, CYP2C21 demonstrated selectivity for formation of the benzylic hydroxylation product and a high estimated f(m,CYP) value. The findings suggest that canine CYP2C21, unlike human CYP2C9, does not derive ligand binding affinity from an anion binding interaction with sulfaphenazole analogs. |
| معلومات مُعتمدة: | R01 GM084546 United States GM NIGMS NIH HHS; GM084546 United States GM NIGMS NIH HHS |
| المشرفين على المادة: | 0 (Molecular Probes) 0 (Recombinant Proteins) 0J8L4V3F81 (Sulfaphenazole) 9035-51-2 (Cytochrome P-450 Enzyme System) EC 1.- (cytochrome P-450 2C2) |
| تواريخ الأحداث: | Date Created: 20120320 Date Completed: 20120716 Latest Revision: 20211021 |
| رمز التحديث: | 20240829 |
| DOI: | 10.2174/187231211798472539 |
| PMID: | 22423626 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1874-0758 |
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| DOI: | 10.2174/187231211798472539 |