Small-molecule inhibitor: cilastatin

Name

History: Cilastatin was developed as an inhibitor of membrane dipeptidase, which is responsible for the in vivo destruction of imepenem and similar beta-lactam antibiotics, to be co-administered with the antibiotics in the clinical situation (Kahan et al., 1983).
Peptidases inhibited: Membrane dipeptidase. The non-peptidase, bacterial metallo-beta-lactamase CphA is also inhibited (Keynan et al., 1995).
Mechanism: Inhibition is reversible. The structure of the complex between cilastatin and membrane dipeptidase has been described by Nitanai et al. (2002), and the structural analogy between cilastatin and diverse substrates of membrane dipeptidase is discussed by Smyth (2004).
Pharmaceutical relevance: Cilastatin is co-administered with antibiotics that are subject to hydrolysis by membrane dipeptidase to potentiate their activity in vivo.
DrugBank: DB01597

CID at PubChem: 54689
ChEBI: 143261
Structure
Chemical/biochemical name: sodium 7-(2-amino-2-carboxy-ethyl)sulfanyl-2-(2,2-dimethylcyclopropyl)carbonylamino-hept-2-enoate
Formula weight: 358