57-Isoform cytochromes P450 for bioconversions

There are likely to be up to 4500 isoforms of CYP in biota, including 57 in human tissues for isoform substrate specificities. These isoforms display differential inhibition by a wide range of biochemical drug-candidates. Drugs are targeted to CYP19 (aromatase) and CYP17 (17α-hydroxylase of sterols). The CYP19 isoform is rate limiting in oestrogen production in the body as it controls the biotransformation of testosterone to oestradiol by aromatisation of steroid ring A. A range of azoles is being developed for treatment of breast cancer by targeting the CYP19 (aromatase) isoform that catalyses the formation of an aromatic ring A as required for the conversion of testosterone to oestradiol. In addition, CYP17 (17α-hydroxylase of pregnenolone and of progesterone) is targeted by a range of drugs for the treatment of prostate cancer. Inhibitor-CYP comparisons are recommended therefore for CYP19 and CYP17 in silico and real-lab so as to continue the development for instance of therapeutic azole inhibitors of CYP19 (aromatase) such as anastrozole, by recognition in silico of quantitative structure/activity relationships (QSARs) between such therapeutic drugs and CYP-utilising pathways.