In 1897, Felix Hoffmann at Bayer acetylated the phenolic –OH of salicylic acid to produce acetylsalicylic acid — less irritating, equally effective. Bayer marketed it as "Aspirin" in 1899. Over the following 125 years, approximately 120 billion tablets have been produced.
The mechanism: irreversible covalent COX inhibition
Aspirin irreversibly acetylates a serine residue (Ser-530 in COX-1, Ser-516 in COX-2) in the hydrophobic channel of cyclooxygenase. The acetyl group of acetylsalicylic acid transfers to the serine –OH, physically blocking arachidonic acid access to the catalytic site. This irreversible inhibition has profound practical consequences — especially for platelets.
In nucleated cells: Acetylated COX degrades and the cell synthesizes new COX within 4–6 hours. In platelets: No nucleus, no protein synthesis. One aspirin dose inhibits platelet COX-1 for the entire platelet lifespan (8–10 days), blocking thromboxane A₂ production permanently. This is why low-dose aspirin (75–100 mg/day) is an effective antiplatelet agent at doses that barely affect COX-2 in other tissues.
Four effects from one enzyme
All four effects of aspirin (analgesia, antipyresis, anti-inflammation, antiplatelet) derive from the same mechanism: inhibition of COX → reduced prostaglandin and thromboxane synthesis. The selectivity for each effect depends on dose, COX isoform, and tissue.
Colorectal cancer chemoprevention
Regular aspirin users consistently show lower colorectal cancer incidence. Mechanism: COX-2 is overexpressed in colorectal neoplastic epithelium; its prostaglandins promote proliferation. Clinical trials confirm ~20% reduction in colorectal adenoma incidence with low-dose aspirin — though chronic use increases GI bleeding risk, reserving the recommendation for high-risk individuals.