Hits identified in library screening demonstrate selective CYP17A1 lyase inhibition

A screening of structurally different steroid hormone synthesis inhibitors was performed in order to find a starting point for the development of a new inhibitor of the bifunctional steroidogenic enzyme CYP17A1. Emphasis was placed on determination of selectivity between the two catalytic steps, namely 17α-hydroxylase and C17,20-lyase. For that purpose a new inhibition assay has been developed. Hits identified within this novel assay demonstrated selective inhibition of CYP17A1 lyase activity, and thus mark the basis for the development of selective C17,20-lyase inhibitors for the treatment of prostate cancer.

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► CYP17A1 lyase activity can be selectively inhibited over 17α-hydroxylase activity.
► Selective lyase inhibitors are identified with new assays.
► The novel lead structure may lay the basis for a safer prostate cancer therapy.
► A new and rapid screening procedure is reported.