FK-506-13C-d2

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.¹ 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.² 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.³ 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⁺.

1.Schreiber, S.L.Chemistry and biology of the immunophilins and their immunosuppressive ligandsScience251(4991)283-287(1991) 2.Dumont, F.J.FK506, An immunosuppressant targeting calcineurin functionCurr. Med. Chem.7(7)731-748(2000) 3.Snyder, S.H., Sabatini, D.M., Lai, M.M., et al.Neural actions of immunophilin ligandsTrends Pharmacol. Sci.19(1)21-26(1998)