Stable expression of polymorphous forms of human cytochrome p450 2d6 as an analytic in the pre-clinical development of medicaments

摘要

Test system comprising cells expressing a cytochrome P450 2D6 (hCYP2D6) allele heterolog, and at least three P450 2D6 alleles are expressed in the system, is new. Independent claims are also included for the following: (1) screening for substances metabolized by human cytochrome P450 2D6, comprising contacting cells of the test system with a substance and measuring metabolite products; (2) determining new P450 2D6 alleles, comprising heterologous expression of the allele in question in a cell and comparing P450 2D6-dependent metabolism in this cell with cells of the test system; and (3) quantifying cytochrome P450 content, comprising solubilizing P450 cytochromes with a non-ionizing detergent Emulgen 913, centrifugation and measurement by CO difference spectra.