Cilastatin

Cilastatin (CAS No.: 82009-34-5) is a selective, reversible inhibitor of renal dehydropeptidase I (DHP-I), a membrane-bound dipeptidase responsible for the hydrolytic metabolism of certain β-lactam antibiotics and the conversion of leukotriene D4 to leukotriene E4, thereby positioning cilastatin as a key pharmacological adjunct in antibacterial therapy and inflammation-related biochemical studies. It exhibits potent inhibitory activity against human and animal DHP-I in the submicromolar to low micromolar range, and additionally demonstrates weaker inhibition of bacterial metallo-β-lactamases such as CphA at higher micromolar concentrations, supporting its utility in mechanistic studies of enzyme inhibition and antibiotic resistance. By blocking renal metabolism of imipenem, cilastatin prolongs antibiotic half-life and enhances systemic exposure, a principle widely leveraged in combination drug formulations for the treatment of severe bacterial infections. Beyond its enzymatic inhibition profile, cilastatin has shown protective effects against drug-induced nephrotoxicity in renal epithelial cell models, suggesting relevance for studies on renal injury, apoptosis, and cytoprotection. In vivo, co-administration with β-lactam antibiotics improves therapeutic efficacy in infection models involving both Gram-positive and Gram-negative pathogens. As a research tool, cilastatin is commonly applied in biochemical assays, cell-based systems, and animal studies investigating renal enzyme function, antibiotic pharmacokinetics, and host-pathogen interactions, with experimental concentrations or dosing regimens tailored to specific study designs.