FK-506

FK-506

Calcineurin (PP-2B) Inhibitor - Immunosuppressant

Product#:

F-900

Sizes:

1 mg

5 x 1 mg

FK 506 (Tacrolimus), a macrolide compound isolated from Streptomyces tsukubaensis, is potent immunosuppressive compounds that inhibit T-cell activation and an inhibitor of fungal growth (10 to 100 times more potent than Cyclosporin A).^1-3 FK-506 binds and inhibits, in vitro the activity of immunophilin proteins known as FK 506-binding protein (FKBP), in a variety of organisms, ranging from yeast to humans.^4-8 Immunosuppression activity of FK-506 seems to be due to FK-506/FKBP complex that inhibits the heterodimeric Ca²⁺ /calmodulin-dependent phosphatase Calcineurin. This, in turn, prevents the Calcineurin-dependent activation of interleukin-2 transcription and T-cell proliferation.^9-12 FK-506 inhibits FKBP activities increases sarcoplasmic reticulum Ca²⁺ release and decrease the ability of Na⁺-Ca²⁺ exchange to extrude Ca²⁺ from the cell.¹³

M.W.:

804.03

CAS No.:

104987-11-3

Structure:

.

Purity:

>98%

Bioassay:

The biological activity was tested to confirm the ability of FK-506 to inhibit the anti-adipogenic effect of Calcineurin in 3T3-L1 cells.

* Not for sale in Germany. 3T3-L1 preadipocytes were induced to undergo adipocyte differentiation with 1mg/ml insulin for 4 days (A, B and C). As indicated cells were additionally treated for the first 4 days of differentiation with 1 mM ionomycin (B and C ) in presence (C) or absence (A and B) of 5 ng/ml FK-506. After 10 days the cells stained with Oil Red O and visualized with light microscopy. A. Control. B. Ionomycin stimulated Calcineurin C. Ionomycin and FK-506.

References:

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2.	Kino, T. et al. (1987) J Antibiot. 40, 1256.
3.	Goto, T. et al. (1991) Transplant Proc. 23, 2713.
4.	Rosen, M.K. and Schreiber, S.L. (1992) Angew. Chem. Int. Ed. Engl. 31, 384.
5.	Schreiber, S.L. et al. (1992) Immunol Today. 13, 136.
6.	Harding, M.W. et al. (1989) Nature. 341, 758.
7.	Bierer, B. et al. (1990) Science. 250, 556.
8.	Jin, Y. et al. (1991) PNAS 88, 6677.
9.	Schreiber, S.L. et al. (1992) Immunol Today. 13, 136.
10.	Liu, J. et al. (1991) Cell 66, 807.
11.	O'Keefe, S.J. et al. (1992) Nature (London) 357, 692.
12.	Dumont , F.J. et al. (1992) Journal of Experimental Medicine 176, 751.
13.	McCall, E. et al. (1996) Circ. Res. 79, 1110.