Sirolimus prevents allograft rejection through which mechanism?
- A Inhibition of calcineurin, blocking IL-2 transcription
- B Inhibition of de novo purine synthesis
- C Blockade of mTOR signalling, preventing IL-2 driven T-cell proliferation ✓
- D Competitive inhibition of guanine nucleotide synthesis
Correct answer: C. Blockade of mTOR signalling, preventing IL-2 driven T-cell proliferation
Explanation
Sirolimus binds FK-binding protein 12 but, unlike tacrolimus, does not inhibit calcineurin; the complex inhibits mTOR kinase, blocking signal transduction required for IL-2 driven clonal T-cell proliferation. Calcineurin inhibition describes cyclosporine and tacrolimus. De novo purine synthesis blockade describes mycophenolate mofetil, and guanine synthesis antagonism describes azathioprine metabolites.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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