Sirolimus and tacrolimus both bind the same intracellular immunophilin protein, yet they block T-cell activation by completely different downstream mechanisms. The shared binding protein and the pathway inhibited by sirolimus are:

• A FKBP12; inhibition of calcineurin phosphatase activity
• B FKBP12; inhibition of mammalian target of rapamycin (mTOR) ✓
• C Cyclophilin; inhibition of IL-2 gene transcription
• D Cyclophilin; blockade of the IL-2 receptor alpha chain

Explanation

Both sirolimus and tacrolimus bind FKBP12, but the sirolimus-FKBP12 complex inhibits mTOR, blocking IL-2 driven signal transduction and arresting the T cell in G1. The tacrolimus-FKBP12 complex instead inhibits calcineurin and prevents IL-2 transcription. Cyclophilin is the target protein of cyclosporine, and CD25 blockade is the mechanism of basiliximab, so options A, C and D are each internally mismatched.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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