Vitamin D receptor ligand EB1089 induced significant expression of genes involved in androgen metabolism in androgen-dependent prostate cancer cell culture experiments, as well as reducing cell proliferation. EB1089 treatment enhanced turnover of testosterone and DHEA—substrates for intracrine conversion to androgen—to their biologically inactive forms. This response was linked to increased CYP3A expression and activity, and inhibition of CYP3A blocked the antiproliferative response to EB1089. This agonist could potentially complement other antiandrogenic drugs, such as abiraterone.
References
Doherty, D. et al. Vitamin D receptor agonist EB1089 is a potent regulator of prostatic “intracrine” metabolism. Prostate 10.1002/pros.22748
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Vitamin D receptor agonist reduces intracrine androgens. Nat Rev Urol 11, 4 (2014). https://doi.org/10.1038/nrurol.2013.295
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DOI: https://doi.org/10.1038/nrurol.2013.295