81129-83-1

Basic information

• Product Name: Cilastatin sodium
• Synonyms: 2-heptenoicacid,7-((2-amino-2-carboxyethyl)thio)-2-(((2,2-dimethylcyclopropyl;l642957;monosodiumsalt,(r-(r*,s*(z)))-)carbonyl)amino);sodium hydrogen [R-[R*,S*-(Z)]]-7-[(2-amino-2-carboxylatoethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]hept-2-enoate;Cilastatine;Cilastatin sodium;Sodium 7-(2-amino-2-carboxy-ethyl)sulfanyl-2-(2,2-dimethylcyclopropyl)carbonylamino-hept-2-enoate;Sodium hydrogen 7-[(2-amino-2-carboxylatoethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]hept-2-enoate
• CAS NO: 81129-83-1
• Molecular Formula: C16H25N2O5S.Na
• Molecular Weight: 380.44
• EINECS: 279-694-4
• Product Categories: Miscellaneous Enzyme
• Mol File: 81129-83-1.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 655.5 °C at 760 mmHg
• Flash Point: 87℃
• Appearance: /
• Vapor Pressure: 7.13E-19mmHg at 25°C
• Storage Temp.: Desiccate at -20°C
• Solubility: Very soluble in water and in methanol, slightly soluble in anhydrous ethanol, very slightly soluble in dimethyl sulfoxide, practically insoluble in acetone and in methylene chloride.
• PKA: pKa1 2.0; pKa2 4.4; pKa3 9.2(at 25℃)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: Cilastatin sodium(CAS DataBase Reference)
• NIST Chemistry Reference: Cilastatin sodium(81129-83-1)
• EPA Substance Registry System: Cilastatin sodium(81129-83-1)

Safety Data

• RTECS: MJ9650200
• Hazardous Substances Data: 81129-83-1(Hazardous Substances Data)

Usage

Description

Cilastatin sodium, also known as monosodium cilastatin, is a nephroprotective dipeptidase inhibitor. It is an off-white to yellowish-white, hygroscopic, amorphous compound derived from heptenoic acid with a molecular mass of 380.43 g. Cilastatin sodium inhibits the proteolytic conversion of leukotriene D4 to E4 and suppresses the invasion and metastasis of DPEP1-expressing tumor cells.

Uses

Used in Pharmaceutical Industry:
Cilastatin sodium is used as an antibacterial adjunct for extending the half-life of β-lactam antibiotics. It inhibits the mammalian β-lactamase renal dipeptidase (dehydropeptidase-1, DPEP1), thereby preventing the renal metabolism of antibiotics like imipenem to microbiologically inactive and potentially nephrotoxic products.
Additionally, Cilastatin sodium is used to inhibit bacterial metallo-β-lactamase, which may block resistance to the carbapenem family of antibiotics in certain bacteria. This application helps in the development of more effective antibiotic treatments and combats antibiotic resistance.

Biological Activity

Dipeptidase inhibitor (LTDase, leukotriene D4 hydrolase, dehydropeptidase I) that displays a K i value of 0.11 μ M. Inhibits metabolism of LTD 4 to LTE 4 and the hydrolysis of β -lactam antibiotics. Nephroprotective; reduces toxic accumulation of cyclosporin A in kidney proximal tubule epithelial cells.

Biochem/physiol Actions

Inhibitor of the renal enzyme dehydropeptidase I and some bacterial zinc-containing β-lactamases. By these action, cilastatin suppresses both host and target metabolism of the broad-spectrum antibiotic imipenem, improving its efficacy.

References

1) White?et al.?(1999),?A continuous fluorometric assay for Leukotriene D4 hydrolase; Anal. Biochem.,?268?245 2) Graham?et al.?(1987),?Inhibition of the mammalian beta-lactamase renal dipeptidase (dehydropeptidase-I) by (Z)-2-acylamino-3-substituted propenoic acids; J. Med. Chem.,?30?1074 3) Keynan?et al. (1995),?The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA; Antimicreob. Agents Chemother.,?39?1629 4) Park?et al.?(2016),?Dehydropeptidase 1 promotes metastasis through regulation of E-cadherin expression in colon cancer; Oncotarget,?7?9501

InChI:InChI=1/C16H26N2O5S.Na/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);/q;+1/p-1/b12-6-;/t10-,11+;/m1./s1