MDV3100

MDV3100 is an experimental androgen receptor antagonist drug developed by the pharmaceutical company Medivation for the treatment of hormone-refractory prostate cancer currently in Phase 3 clinical trials. Results so far have been encouraging; Medivation has reported up to an 89% decrease in prostate specific antigen serum levels after a month of taking the medicine.

Preclinical pharmacology
MDV3100 has approximately fivefold higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide. As opposed to bicalutamide, MDV3100 does not promote translocation of AR to the nucleus and in addition prevents binding of AR to DNA and AR to coactivator proteins.

When LNCaP cells (a prostate cancer cell line) were treated with MDV3100, the expression of androgen dependent  genes PSA and TMPRSS2 was down regulated in contrast to bicalutamide where the expression was upregulated. In VCaP cells which over express androgen receptors, MDV3100 induced apoptosis whereas bicalutamide did not. Furthermore MDV3100 behaves as an antagonist of the W741C mutant androgen receptor in contrast to bicalutamide which behaves as a pure agonist when bound to the W741C mutant.

Clinical studies
MDV 3100 was found clinically active for metastatic castration-resistant prostate cancer patients in a phase II trial. PSA level decreased more than 50 percent in 40/65 chemo-naive patients and 38/75 chemotherapy-trated patients.

Medivation is conducting an international phase III trial beginning in September 2009. In addition, there is an additional phase II study commencing in 2010 that will compare mdv3100 with bicalutamide in hormone-naive metastatic prostate cancer patients.