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• W2007703732 abstract "The pregnene derivative, 4-pregnene-3-one-20β-carboxaldehyde (22-A) was evaluated as an inhibitor of 17α-hydroxylase/C17,20-lyase in rat testicular microsomes and of 5α-reductase in human prostatic homogenates. The effect of the compound in vivo was studied in adult male rats. The 22-A demonstrated potent and competitive inhibition of 17α-hydroxylase and C17,20-lyase with Ki values 8.48 and 0.41 μM, respectively, significantly below the Km values for these two enzymes (33.75 and 4.55 μM). This compound also showed potent inhibition of 5α-reductase with a Ki value of 15.6 nM (Km for this enzyme is 50 nM). By comparison, ketoconazole, a currently studied 17α-hydroxylase/C17,20-lyase inhibitor for the treatment of prostatic cancer, showed less potent inhibition of 17α-hydroxylase (Ki 39.5 μM) and C17,20-lyase (Ki 3.6 μM) and did not inhibit 5α-reductase. Progesterone which has been reported to inhibit the 17α-hydroxylase/C17,20-lyase, did not significantly reduce the production of testosterone by rat testes in vitro in comparison to controls, while the same concentration of 22-A demonstrated a 42% reduction of testosterone biosynthesis. When the adult male rats were injected s.c. with 22-A at 50 mg/day/kg for a 2 week period, the testosterone concentrations in the rat sera were significantly lower than control values (P < 0.05), whereas serum corticosterone levels did not change. These results suggest that 22-A is a selective potent inhibitor for 17α-hydroxylase and C17,20-lyase, but is more potent for the C17,20-lyase. The compound also inhibits 5α-reductase, and therefore may reduce biosynthesis of testosterone and dihydrotestosterone effectively. Thus, 22-A may be useful in the treatment of problems associated with the androgen excess and prostatic cancer." @default.
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• W2007703732 date "1992-05-01" @default.
• W2007703732 modified "2023-10-14" @default.
• W2007703732 title "4-pregnene-3-one-20β-carboxaldehyde: A potent inhibitor of 17α-hydroxylase/C17,20-lyase and of 5α-reductase" @default.
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• W2007703732 doi "https://doi.org/10.1016/0960-0760(92)90134-5" @default.
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