• Corpus ID: 8323360

Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase).

  title={Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase).},
  author={S. Elaine Barrie and Gerard Andrew Potter and Phyllis M. Goddard and Ben P. Haynes and Mitch Dowsett and Michael Ian Jarman},
  journal={The Journal of steroid biochemistry and molecular biology},
  volume={50 5-6},
Medical or surgical castration for the treatment of prostatic cancers prevents androgen production by the testes, but not by the adrenals. Inhibition of the key enzyme for androgen biosynthesis, cytochrome P450(17) alpha, could prevent androgen production from both sources. The in vivo effects of 17-(3-pyridyl)androsta-5,16-dien-3 beta-ol (CB7598) and 17-(3-pyridyl)androsta-5,16-dien-3-one (CB7627), novel potent steroidal inhibitors of this enzyme, on WHT mice were compared with those of… 
Novel Steroidal Inhibitors of Human Cytochrome P45017α (17α -Hydroxylase-C17,20-lyase): Potential Agents for the Treatment of Prostatic Cancer.
Steroidal compounds having a 17-(3-pyridyl) substituent together with a 16,17-double bond have been synthesized, using a palladium-catalyzed cross-coupling reaction of a 17-enol triflate with
Molecular Pathways: Inhibiting Steroid Biosynthesis in Prostate Cancer
Given the drawbacks of 17α-hydroxylase inhibition, there is considerable interest in developing new CYP17A1 inhibitors that more specifically inhibit lyase activity and are therefore less likely to require glucocorticoid coadministration.
Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer
It is demonstrated that CYP17 inhibitors, with the exception of orteronel, can function as competitive AR antagonists and observed that seviteronel and abiraterone inhibited the growth of tumor xenografts expressing the clinically relevant mutation AR-F876L and that this activity could be attributed entirely to competitive AR antagonism.
Inhibitors of steroidogenesis as agents for the treatment of hormone-dependent cancers
The progress made in developing of clinically useful steroidogenesis inhibitors for the relevant disease is discussed and some of the difficulties encountered in maintaining/achieving remission due to the changing nature of the disease are discussed.
Determination of Novel Metabolites of Therapeutic Agents used in the Treatment of Castration-Resistant Prostate Cancer
This project aimed to investigate the steroidogenic metabolism of abiraterone and galeterone and evaluate the metabolites’ role in prostate cancer and develop and validation of a liquid chromatography mass spectrometry method LC-MS/MS to determine abiraters metabolites.
Anticancer Activity of a Novel Selective CYP17A1 Inhibitor in Preclinical Models of Castrate-Resistant Prostate Cancer
Preclinical results suggest greater suppression of the AR axis with VT-464 than ABI that is likely due to both superior selective suppression of androgen synthesis and AR antagonism.
Targeting CYP17: established and novel approaches in prostate cancer.
Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven.
  • G. Attard, A. Reid, J. D. de Bono
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2008
CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC, and data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.
Synthesis and Characterization of Microbial Metabolites of Abiraterone Acetate and an Evaluation of Their Anticancer Activity against Breast Cancer Cell Line MCF-7
Higher quantities of new microbial metabolites of the anticancer drug, Abiraterone acetate, were synthesized using fungi and then purified by column chromatography, showing >99% purity on HPLC and exhibited good cytotoxicity compared to the parent drug.