Cilastatin

Cilastatin

Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a686013
Routes of administration	IV
ATC code	J01DH51 (WHO) (combination with imipenem)
Identifiers
IUPAC name (Z)-7-[(2R)-2-Amino-3-hydroxy-3-oxopropyl]sulfanyl-2-{[(1S)-2,2-dimethylcyclopropanecarbonyl]amino}hept-2-enoic acid
CAS Number	82009-34-5 Y
PubChem (CID)	5280454
IUPHAR/BPS	5166
DrugBank	DB01597 Y
ChemSpider	4940183 Y
UNII	141A6AMN38 Y
KEGG	D07698 Y
ChEBI	CHEBI:3697 Y
ChEMBL	CHEMBL766 Y
ECHA InfoCard	100.072.592
Chemical and physical data
Formula	C16H26N2O5S
Molar mass	358.454 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(N\C(=C/CCCCSC[C@@H](C(=O)O)N)C(=O)O)[C@H]1CC1(C)C
InChI InChI=1S/C16H26N2O5S/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23)/b12-6-/t10-,11+/m1/s1 Y Key:DHSUYTOATWAVLW-WFVMDLQDSA-N Y
(verify)

Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase.^[1]

Dehydropeptidase is an enzyme found in the kidney and is responsible for degrading the antibiotic imipenem. Cilastatin can therefore be combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. Imipenem alone is an effective antibiotic and can be given without the cilastatin. Cilastatin itself does not have antibiotic activity although it has been proved to be active against a zinc-dependent beta-lactamase that usually confer antibiotic resistance to certain bacteria; more precisely the carbapenem family of antibiotics. This property is due to the physico-chemical similarities between membrane dipeptidase (MDP), the compound it is usually set to target, and the bacterial metallo-beta-lactamase carried by the CphA gene^[1] Therefore, cilastatin is considered a beta-lactamase inhibitor, not an antibiotic per se. But as with other combinations of an antibiotic with an enzyme inhibitor, the combination allows the antibiotic to be more effective by changing the pharmacokinetics involved. Thus imipenem/cilastatin, like amoxicillin/clavulanic acid, is a commonly used combination product.

References