Tacrolimus
Macrolide calcineurin inhibitor from Streptomyces tsukubaensis used as an immunosuppressant in organ transplantation and atopic dermatitis.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C44H69NO12 |
| Molecular Weight | 804.02 Da |
| CAS Number | 104987-11-3 |
| Peptide Class | Macrolide Lactone |
| Origin | Streptomyces tsukubaensis |
Structure
Tacrolimus (FK506) is a 23-membered macrolide lactone produced by Streptomyces tsukubaensis. Despite being a macrolide rather than a classical peptide, it contains a hemiketal-masked alpha,beta-diketoamide portion and several stereochemical features typical of nonribosomal peptide products. The molecule is highly lipophilic.
Mechanism of Action
Tacrolimus binds to FKBP12 (FK506-binding protein), and the tacrolimus-FKBP12 complex inhibits calcineurin, the calcium-calmodulin-dependent phosphatase. This prevents NFAT dephosphorylation and nuclear translocation, blocking IL-2, IL-4, and TNF-alpha transcription, thereby suppressing T-cell activation and proliferation.
Clinical Applications
- Organ transplantation: Prevention of rejection (kidney, liver, heart, lung)
- Atopic dermatitis: Topical for moderate-to-severe disease
- Autoimmune diseases: Refractory uveitis, myasthenia gravis
- Graft-versus-host disease: Prophylaxis and treatment
Pharmacokinetics
- Half-life: 12-15 hours
- Tmax: 1-3 hours (oral)
- Bioavailability: 20-25% (variable)
- Metabolism: CYP3A4 (extensive)
- Protein binding: 75-99%
- Route: Oral, IV, topical
Safety and Side Effects
Nephrotoxicity, diabetes mellitus (new-onset), neurotoxicity (tremor, headache, seizures), hypertension, hyperkalemia, hypomagnesemia, and increased infection/malignancy risk. Narrow therapeutic index with extensive drug interactions.
References
- Goto, T., et al. (1987). FK506: a novel immunosuppressant. Progress in Transplantation, 4, 1-11.
- Kino, T., et al. (1987). FK506, a novel immunosuppressant from Streptomyces. Journal of Antibiotics, 40, 1249-1255.
Test Your Knowledge
Reinforce what you learned about Tacrolimus with interactive quizzes on Wikipept.
Take a Quiz on Wikipept