Suicide inhibition

Examples

• Disulfiram, which inhibits the acetaldehyde dehydrogenase enzyme.
• Aspirin, which inhibits cyclooxygenase 1 and 2 enzymes.
• Clavulanic acid, which inhibits β-lactamase: clavulanic acid covalently bonds to a serine reside in the active site of the β-lactamase, restructuring the clavulanic acid molecule, creating a much more reactive species that attacks another amino acid in the active site, permanently inactivating it, and thus inactivating the enzyme β-lactamase.
• Penicillin, which inhibits DD-transpeptidase from building bacterial cell walls.
• Sulbactam, which prohibits penicillin-resistant strains of bacteria from metabolizing penicillin.
• AZT and other chain-terminating nucleoside analogues used to inhibit HIV-1 reverse transcriptase in the treatment of HIV/AIDS.
• Eflornithine, one of the drugs used to treat sleeping sickness, is a suicide inhibitor of ornithine decarboxylase.
• Nerve agent and related pesticides such as parathion are organophosphorus suicide inhibitors of acetylcholinesterase with aging times dependent on the lability of leaving groups present on the organophosphorus moiety of the molecule.
• 5-fluorouracil acts as a suicide inhibitor of thymidylate synthase during the synthesis of thymine from uridine. This reaction is crucial for the proliferation of cells, particularly those that are rapidly proliferating. By inhibiting this step, cells die from a thymineless death because they have no thymine to create more DNA. This is often used in combination with methotrexate, a potent inhibitor of dihydrofolate reductase enzyme.
• O⁶-Benzylguanine, a drug which depletes O6-alkylguanine-DNA alkyltransferase by virtue of its similarity to the DNA repair protein's target lesion.
• Exemestane, a drug used in the treatment of breast cancer, is an inhibitor of the aromatase enzyme.
• Selegiline, although in the attached reference the compound is called a 'suicide inactivator'.
• Vigabatrin, an anticonvulsant, is a suicide inhibitor of GABA-T.

  Rational drug design