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 (Ki = 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+.
