Abstract:
:Steroid derivatives bearing fluorescent groups such as anthracene, dansyl, deazaflavin, and pyrene attached to C6 were synthesized. These compounds are unique inhibitors of cytochrome P450 3A4 (CYP3A4) and display similar IC(50) values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipine. On binding to CYP3A4, the fluorescence of the dansyl, deazaflavin, and pyrene probes is quenched by photophysical interaction of the fluorophore with the heme. The addition of drug candidates with binding constants in the nM-microM range causes displacement of the probes from the active site, and hence leads to restoration of fluorescence. Accordingly, relative affinities of drug candidates to CYP3A4 can be easily and accurately determined by fluorescence measurements.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Chougnet A,Grinkova Y,Ricard D,Sligar S,Woggon WDdoi
10.1002/cmdc.200600300subject
Has Abstractpub_date
2007-05-01 00:00:00pages
717-24issue
5eissn
1860-7179issn
1860-7187journal_volume
2pub_type
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