Molecular properties and CYP2D6 substrates: central nervous system therapeutics case study and pattern analysis of a substrate database.

ABSTRACT: CYP2D6 substrate status is a critical Go/No Go decision criteria in central nervous system (CNS) drug discovery efforts because the polymorphic nature of CYP2D6 can lead to variable patient safety and drug efficacy. In addition, CYP2D6 is disproportionately involved in the metabolism of CNS drugs compared with other drug classes. Therefore, identifying trends in small molecule properties of CNS-penetrant compounds that can help discriminate potential CYP2D6 substrates from nonsubstrates would allow additional prioritization in the synthesis and biological evaluation of new therapeutic candidates. We report here the conversion of the CNS drug minaprine from substrate to nonsubstrate, as well as the conversion of the related CNS drug minozac from nonsubstrate to substrate, through the use of

SUBMITTER: Chico LK 

PROVIDER: S-EPMC2774985 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature