| Bioactivity | CYP3cide (PF-4981517) is a potent, selective and time-dependent inhibitor of cytochrome P4503A4 (CYP3A4). The IC50 values for Midazolam 1’-hydroxylase activity are 0.03 μM, 17 μM, and 71 μM for CYP3A4, CYP3A5, and CYP3A7, respectively. CYP3cide can be used to distinguish the contributions of CYP3A4 versus CYP3A5 on drug metabolism[1]. | |||||||||
| Invitro | When investigating the inhibitory properties of CYP3cide, an extreme metabolic inactivation efficiency (kinact/KI) of 3300 to 3800 ml • min-1 • μmol-1 is observed using human liver microsomes from donors of nonfunctioning CYP3A5 (CYP3A5 *3/*3). This observed efficiency equated to an apparent KI between 420 and 480 nM with a maximal inactivation rate (kinact) equal to 1.6 min-1. When CYP3cide is tested at a concentration and preincubation time to completely inhibit CYP3A4 in a library of genotyped polymorphic CYP3A5 microsomes, the correlation of the remaining midazolam 1'-hydroxylase activity to CYP3A5 abundance is significant[1]. | |||||||||
| Name | CYP3cide | |||||||||
| CAS | 1390637-82-7 | |||||||||
| Formula | C26H32N8 | |||||||||
| Molar Mass | 456.59 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [1]. Robert L Walsky, et al. Selective mechanism-based inactivation of CYP3A4 by CYP3cide (PF-04981517) and its utility as an in vitro tool for delineating the relative roles of CYP3A4 versus CYP3A5 in the metabolism of drugs. Drug Metab Dispos. 2012 Sep;40(9) |