Recent Events
January: Nature Paper Published
Structures of Human Cytochrome P450 17A1:
Insights into Drug Design for Prostate and Breast Cancers
- Cytochrome P450 17A1 (CYP17A1) performs sequential hydroxylase and lyase reactions essential for the production of steroid hormones called androgens and estrogens.
- Prostate cancer and breast cancer proliferate in response to androgens and estrogens, respectively.
- Thus, inhibition of CYP17A1 is a new approach to treating prostate and breast cancer, but no structures of CYP17A1 were previously available to assist in drug design.
- The first structures of CYP17A1 are complexes with drugs either recently approved by the FDA for metastatic
prostate cancer (abiraterone or Zytiga®) or currently in clinical trials (TOK-001 or Galeterone®). These structures:
- demonstrate that both drugs bind more perpendicular to the heme, rather than the parallel orientation proposed
- reveal important opportunities to improve drug design
- demonstrate similarities to steroid receptors that are likely the basis for the dual mechanism of action for TOK-001 at the androgen receptor
- elucidate the structural roles of many mutations found in patients with diseases called 17-hydroxylase deficiencies
See the KU Press Release
Graphic design (above) by Jing Jian
Structures of the human steroidogenic membrane cytochrome P450 17A1 are published in Nature:
DeVore, N.M. and Scott, E.E. Cytochrome P450 17A1 structures with prostate cancer drugs abiraterone
and TOK-001. Nature. DOI: 10.1038/nature10743.