FK-506

• CAT Number: I000276
• CAS Number: 104987-11-3
• Molecular Formula: C44H69NO12
• Molecular Weight: 804.02
• Purity: ≥95%
• Synonyms: Protopic; Fujimycin; tacrolimus
• Target: Antibiotic
• Solubility: DMSO: ≥ 28 mg/mL
• Storage: 3 years -20C powder
• IC50: 0.47 nM (Inhibition of lymphocyte proliferation)
• IUPAC Name: (1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-1,14-dihydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-17-prop-2-enyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
• InChI: InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/
• InChIKey: QJJXYPPXXYFBGM-LFZNUXCKSA-N
• SMILES: CC1CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC(=O)C(C=C(C1)C)CC=C)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC

FK-506(CAT: I000276), also known as tacrolimus, is a potent immunosuppressive drug used in organ transplantation to prevent rejection. It is derived from the bacterium Streptomyces tsukubaensis and acts by inhibiting the enzyme calcineurin, which plays a key role in T-cell activation and the immune response. By inhibiting calcineurin, FK-506 suppresses the production of interleukin-2 and other cytokines involved in immune activation. This helps to prevent the immune system from attacking and rejecting transplanted organs.

Overview of Clinical Research

The phase 4 study of  Tacrolimus in transplants is ongoing. It was discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. Tacrolimus is chemically known as a macrolide. It reduces peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This FKBP12-FK506 complex inhibits calcineurin which inhibits T-lymphocyte signal transduction and IL-2 transcription.

Reference

1: Jusko WJ, Kobayashi M. Therapeutic monitoring of tacrolimus (FK 506). Ther Drug Monit. 1993 Aug;15(4):349. PubMed PMID: 7694395.
2: Piekoszewski W, Chow FS, Jusko WJ. Disposition of tacrolimus (FK 506) in rabbits. Role of red blood cell binding in hepatic clearance. Drug Metab Dispos. 1993 Jul-Aug;21(4):690-8. PubMed PMID: 7690698.
3: Piekoszewski W, Jusko WJ. Plasma protein binding of tacrolimus in humans. J Pharm Sci. 1993 Mar;82(3):340-1. PubMed PMID: 7680714.
4: Jegasothy BV, Ackerman CD, Todo S, Fung JJ, Abu-Elmagd K, Starzl TE. Tacrolimus (FK 506)–a new therapeutic agent for severe recalcitrant psoriasis. Arch Dermatol. 1992 Jun;128(6):781-5. PubMed PMID: 1376102; PubMed Central PMCID: PMC3208344.
5: Min DI, Brown T, Hwang GC. Visual compatibility of tacrolimus with commonly used drugs during simulated Y-site injection. Am J Hosp Pharm. 1992 Dec;49(12):2964-6. PubMed PMID: 1282779.