Celecoxib preferentially inhibits COX-2 over COX-1. The structural basis for this selectivity is:
- A Celecoxib's sulfonamide side chain fits only the larger hydrophobic side-pocket unique to COX-2 ✓
- B Celecoxib irreversibly acetylates serine-530 on COX-2 but not COX-1
- C COX-2 lacks the arachidonic acid binding site that COX-1 possesses
- D Celecoxib is a prodrug activated exclusively in inflamed tissue by COX-2 peroxidase activity
Correct answer: A. Celecoxib's sulfonamide side chain fits only the larger hydrophobic side-pocket unique to COX-2
Explanation
COX-2 has a larger active site than COX-1, with a distinctive side-pocket created by the substitution of isoleucine-523 (COX-1) with valine-523 (COX-2). Celecoxib's bulky sulfonamide phenyl group inserts into this COX-2-specific side-pocket, conferring selective inhibition. Aspirin (not celecoxib) irreversibly acetylates serine-530. Both COX isoforms bind arachidonic acid.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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