Journal article
A non-acidic sulfaphenazole analog demonstrating high intrinsic clearance and selectivity by canine CYP2C21
Drug metabolism letters, Vol.5(4), p.253
12/2011
Handle:
https://hdl.handle.net/2376/107153
PMID: 22423626
Abstract
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.
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Details
- Title
- A non-acidic sulfaphenazole analog demonstrating high intrinsic clearance and selectivity by canine CYP2C21
- Creators
- Charles W Locuson - Pfizer Animal Health, Veterinary Medicine Research and Development, Metabolism & Safety, Kalamazoo, MI 49001, USA. charles.w.locuson@pfizer.comJosh F AlfaroMatthew J ZayaDenis BillenJulie A WhiteJeffrey P Jones
- Publication Details
- Drug metabolism letters, Vol.5(4), p.253
- Academic Unit
- Chemistry, Department of
- Publisher
- United Arab Emirates
- Grant note
- GM084546 / NIGMS NIH HHS R01 GM084546 / NIGMS NIH HHS
- Identifiers
- 99900546704401842
- Language
- English
- Resource Type
- Journal article