1356841-89-8

FK-506-¹³C-d₂ contains two deuterium atoms located on the carbon-13 bond. It is intended for use as an internal standard for the quantification of FK-506 by GC- or LC-MS. FK-506 is a potent, clinically-useful immunosuppressant in the same molecular class as cyclosporin A and rapamycin. Its mechanism of action involves the formation of a high affinity complex (K_i = 0.2 nM) with FK-506 Binding Protein 12 (FKBP12). This complex then inhibits the activity of the calcium/calmodulin-dependent protein phosphatase, calcineurin, leading to disruption of T cell activation. The physiological effects of FK-506 also include regulation of nitric oxide neurotoxicity, neurotransmitter release, and regulation of Ca²⁺ release via the ryanodine and inositol-(1,4,5)-trisphosphate (IP₃) receptors. In the latter case, FKBP12 forms a tight complex with both ryanodine and IP₃ receptors which can be disrupted by FK-506, thereby rendering the receptors “leaky” to Ca²⁺.

A labelled immunosuppressant that blocks T cell proliferation in vitro by inhibiting the generation of several lymphokines, especially IL-2. Shown to inhibit the activity of FK-506 binding protein, thereby reversing its effects on sarcoplasmic reticulum Ca+2 release. A representative lot contained a distribution of 20% d-1, 40% d-2 and 20% d-3.

This stable-labeled internal standard is suited for quantitation of tacrolimus by LC/MS or GC/MS for clinical toxicology, therapeutic drug monitoring, or isotope dilution methods. Tacrolimus, also known as FK-506 or fujimycin, is an immunosuppressive drug marketed as Prograf, Advagraf, and Protopic usually used to prevent rejection of organ transplants and treatment of eczema. Use of a stable-labeled analog of tacrolimus is the best choice to minimize variability or mitigate any potential interference in LC-MS/MS analysis.

Macrolide

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