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Determination Of Novel Metabolites Of Therapeutic Agents Used In The Treatment Of Castration-Resistant Prostate Cancer, Mohammad Alyamani
Determination Of Novel Metabolites Of Therapeutic Agents Used In The Treatment Of Castration-Resistant Prostate Cancer, Mohammad Alyamani
ETD Archive
Despite an array of improved treatment options over the past decade, prostate cancer remains the second leading cause of cancer mortality for men in the United States. Abiraterone and galeterone are oral steroidal compounds that are used to treat metastatic castration-resistant prostate cancer (CRPC). Abiraterone blocks 17a-hydroxylase/17,20-lyase (CYP17A1), an enzyme required for androgen synthesis. Galeteron inhibits CYP17A1, blocks the androgen receptor (AR), and decreases AR protein levels. Both drugs share the same structure with endogenous androgens such as dehydroepiandrosterone, which are substrates for the enzyme, 3ß-hydroxysteroid dehydrogenase (3ßHSD). Metabolites of 3ßHSD undergo further metabolism to produce the AR ligand, testosterone …