Inhibitors of P450-dependent steroid biosynthesis: from research to medical treatment.

A number of cytochrome P450-dependent enzymes are major targets for both steroidal and nonsteroidal compounds that may be of use in the treatment of a number of androgen-independent, androgen-, estrogen- and other steroid-dependent diseases. Compounds of interest are for example aminoglutethimide and derivatives; esters of 4-pyridineacetic acid; imidazole derivatives, such as ketoconazole, liarozole, fadrozole, CGS 18320 B; bis-chlorophenyl-pyrimidine analogues; triazole derivatives vorozole and CGS 20267, and steroidal aromatase inhibitors such as 4-hydroxyandrostenedione. Some of them (e.g. ketoconazole) triggered studies to find new possibilities in medical treatment. Others are of use clinically or under clinical evaluation to provide a palliative treatment and/or cure to patients with for example prostatic carcinoma, breast cancer, hypercortisolism and benign prostatic hyperplasia.