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Avoiding PXR and CAR Activation and CYP3A4 Enzyme Induction

Part of the Topics in Medicinal Chemistry book series (TMC,volume 9)

Abstract

Avoiding drug–drug interactions is an important aspect of today’s drug discovery and development process. The most significant of these interactions occur through changes in the enzyme level of CYP3A4 which is involved in the metabolism of many drugs. Increases in the expression of CYP3A4 mRNA and enzyme activity can occur through several mechanisms, the most predominant of which is the activation of transcription factors, such as the nuclear hormone receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Through an understanding of interactions between drugs (ligands) and the ligand binding pockets of these receptors, several laboratories have attenuated the binding interactions and significantly reduced the potential for CYP3A4 induction and ultimately drug–drug interactions.

Keywords

  • Constitutive androstane receptor
  • CYP3A4
  • Drug discovery
  • Drug-drug interactions
  • Pregnane X receptor
  • Structure-activity-relationship

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Sinz, M.W. (2013). Avoiding PXR and CAR Activation and CYP3A4 Enzyme Induction. In: Meanwell, N. (eds) Tactics in Contemporary Drug Design. Topics in Medicinal Chemistry, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7355_2013_24

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