Elsevier

Drug Discovery Today

Volume 2, Issue 11, November 1997, Pages 479-486
Drug Discovery Today

Review
Properties of cytochrome P450 isoenzymes and their substrates part 2: properties of cytochrome P450 substrates

https://doi.org/10.1016/S1359-6446(97)01085-4Get rights and content

Cytochrome P450 isoenzymes are pivotal in drug clearance. Part 1 of this two-part review, published in the October issue of Drug Discovery Today, described the active site characteristics of members of the P450 superfamily. This article describes the great increase in our understanding of the substrate requirements of the human cytochrome P450 family and highlights the relevance of this knowledge for the design of new therapeutic agents.

References (20)

  • SmithD.A.

    Biochem. Pharmacol.

    (1992)
  • SmithD.A.

    Biochem. Pharmacol.

    (1992)
  • FerrariS.

    Life Sci.

    (1991)
  • KoleyA.P.

    J. Biol. Chem.

    (1995)
  • SmithD.A.

    Med. Res. Rev.

    (1996)
  • McManusM.E.

    Cancer Res.

    (1990)
  • LewisD.F.V.

    Drug Metab. Rev.

    (1986)
  • MizukiY.

    Xenobiotica

    (1996)
  • LewisD.F.V.

    Xenobiotica

    (1996)
  • JonesB.C.

    Drug Metab. Dispos.

    (1996)
There are more references available in the full text version of this article.

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