Enzyme inhibition, drug design mechanism-based inhibitors

Mechanism-based irreversible inhibition occurs when a reactive metabolic intermediate is formed in situ that can (1) bind covalently with the prosthetic heme through N-alkyllary-lation (e.g., secobarbital), f"2 alkylate the apo-cytochrome (e.g., chloramphenicol or 2-ethy-nylnaphthalene), or (5) cause destruction of the prosthetic heme to products that irreversibly bind to the apocytochrome (e.g. CCI4) (158). These mechanism-based inactivators have primarily been designed and used for the selective inhibition of specific CYP enzymes and elucidating the mechanism of P450 reactions. Some drugs (e.g., aromatase inhibitors)... 

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