Cytochrome P450 17A1 (CYP17A1) (CYP17A1)

Cytochrome P450 17A1 (CYP17A1) is a key bifunctional enzyme in the human steroidogenic pathway, localized in the endoplasmic reticulum of the adrenal glands and gonads [1, 4]. It catalyzes two distinct reactions: the 17-alpha-hydroxylation of pregnenolone and progesterone, and the subsequent 17,20-lyase reaction that cleaves the C17-C20 bond to produce androgen precursors like dehydroepiandrosterone (DHEA) [2, 11]. These activities are essential for the biosynthesis of both glucocorticoids and sex steroids, making the enzyme a critical regulator of hormonal balance [4, 7]. In clinical medicine, CYP17A1 is a primary therapeutic target for the treatment of metastatic castration-resistant prostate cancer (mCRPC), where it facilitates the production of extratesticular androgens that drive tumor progression [1, 12]. The drug abiraterone acetate is a potent, irreversible inhibitor of CYP17A1 that binds to the enzyme's heme iron, effectively blocking both its hydroxylase and lyase functions [1, 15]. While highly effective at reducing androgen levels, inhibition of CYP17A1 can lead to a buildup of upstream mineralocorticoids, resulting in side effects such as hypertension and hypokalemia [3, 12]. Consequently, patients treated with CYP17A1 inhibitors typically require co-administration of glucocorticoids to prevent adrenal insufficiency and manage mineralocorticoid excess [6, 17]. Beyond prostate cancer, the enzyme is implicated in conditions like congenital adrenal hyperplasia and polycystic ovary syndrome, and it remains a focus for developing more selective non-steroidal inhibitors [3, 13].

Other names

P450c17Steroid 17-alpha-hydroxylase/17,20 lyaseCPT7S17AHSteroid 17-alpha-monooxygenaseCYP17Cytochrome P450-C17

Inhibition of 17-alpha-hydroxylase and 17,20-lyase activities, which prevents the conversion of pregnenolone and progesterone into androgen precursors.