Enzymes as Drug Targets

Why enzymes are pharmacological targets

1. Foundational rationale

• Enzymes are one of four major biomacromolecular target classes for drug action — alongside receptors, ion channels, and transporters (KDT 8e Ch.4, p.45–46)
• ~30% of all human drug targets are enzymes; the other major share is receptors (47%), with channels and transporters making up most of the remainder (G&G 14e Ch.3, p.43–44)
• Enzymes are favoured targets because (i) they have selective, often rate-limiting roles in essential life processes, and (ii) the molecular logic of catalysis and allosteric regulation is sufficiently well-defined to be amenable to rational pharmacological manipulation (G&G 14e Ch.3, p.45)
• The drugs that act on enzymes span virtually every therapeutic area — lisinopril and other ACE-Is, atorvastatin and other HMG-CoA reductase inhibitors, metformin, ibuprofen and other NSAIDs, warfarin, allopurinol, finasteride, apixaban, sitagliptin are explicitly named (G&G 14e Ch.3, p.44)
• A subset of drugs that don't act on classical "regulatory" macromolecules — paracetamol's COX inhibition, statins' HMG-CoA reductase inhibition, allopurinol's xanthine oxidase inhibition, omeprazole's H⁺/K⁺ ATPase inhibition — are sometimes loosely called "non-receptor" because their targets are effector enzymes rather than signalling receptors (KDT 8e Ch.4, p.45)