Cilastatin-15N-d3 is intended for use as an internal standard for the quantification of cilastatin by GC- or LC-MS. Cilastatin is an inhibitor of dipeptidase (dehydropeptidase I), a renal dipeptidase.1 It inhibits human renal dipeptidase (Ki = 0.7 μM), porcine dipeptidase (IC50 = 0.11 μM), and bacterial metallo-β-lactamase CphA from A. hydrophila (IC50 = 178 μM).1,2,3 Cilastatin (200 μg/ml) protects primary porcine renal proximal tubular epithelial cells from nephrotoxicity and apoptosis induced by vancomycin .4 In a mouse model of systemic infection, cilastatin in combination with imipenem protects mice from S. aureus, E. coli, and P. aeruginosa infection.5 Cilastatin was designed to inhibit renal metabolism of imipenem and prolong its half-life.2 Formulations containing cilastatin in combination with imipenem have been used to treat susceptible bacterial infections.
1.Campbell, B.J., Forrester, L.J., Zahler, W.L., et al.Beta-lactamase activity of purified and partially characterized human renal dipeptidaseJ. Biol. Chem.259(23)14586-14590(1984) 2.Kahan, F.M., Kropp, H., Sundelof, J.G., et al.Thienamycin: Development of imipenen-cilastatinJ. Antimicrob. Chemother.12(Suppl. D)1-35(1983) 3.Keynan, S., Hooper, N.M., Felici, A., et al.The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-β-lactamase enzyme CphAAntimicrob. Agents Chemother.39(7)1629-1631(1995) 4.Humanes, B., Jado, J.C., CamaÑo, S., et al.Protective effects of cilastatin against vancomycin-induced nephrotoxicityBiomed Res. Int.2015704382(2015) 5.Petersen, P.J., Jacobus, N.V., Weiss, W.J., et al.In vitro and in vivo activities of LJC10,627, a new carbapenem with stability to dehydropeptidase IAntimicrob. Agents Chemother.35(1)203-207(1991)