Natriumhydrogen-[R-[R,S-(Z)]]-7-[(2-amino-2-carboxylatoethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]hept-2-enoat

Bezeichnung:Natriumhydrogen-[R-[R*,S*-(Z)]]-7-[(2-amino-2-carboxylatoethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]hept-2-enoat

CAS-Nr81129-83-1

Englisch Name:Cilastatin sodium

CBNumberCB8260633

SummenformelC16H25N2O5S.Na

Molgewicht380.44

MOL-Datei81129-83-1.mol

Synonyma

Natriumhydrogen-[R-[R*,S*-(Z)]]-7-[(2-amino-2-carboxylatoethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]hept-2-enoat

Natriumhydrogen-[R-[R*,S*-(Z)]]-7-[(2-amino-2-carboxylatoethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]hept-2-enoat physikalisch-chemischer Eigenschaften

Schmelzpunkt	>160°C (dec.)
Flammpunkt	87℃
storage temp.	2-8°C
Löslichkeit	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.
Aggregatzustand	Solid
pka	pKa1 2.0; pKa2 4.4; pKa3 9.2(at 25℃)
Farbe	White
Biologische Quelle	synthetic (organic)
Wasserlöslichkeit	water: 10mg/mL, clear, colorless to faintly yellow
Stabilität	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 Datenbank	81129-83-1(CAS DataBase Reference)

Sicherheit

RTECS-Nr.	MJ9650200
HS Code	2941.90.1050

Gefahreninformationscode (GHS)

Cilastatin sodium Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Cilastatin Na (81129-83-1) is a dehydropeptidase-1 inhibitor. Inhibits the proteolytic conversion of leukotriene D4?to E4.1? Inhibits the mammalian β-lactamase renal dipeptidase (dehydropeptidase-1, DPEP1) and thus is used as an antibacterial adjunct to extend the half-life of β-lactam antibiotics.2?Cilastatin also inhibits bacterial metallo-β-lactamase and thereby may block resistance to the carbapenem family of antibiotics in certain bacteria.3? Suppresses invasion and metastasis of DPEP1-expressing tumor cells.4
Chemische Eigenschaften
White or light yellow amorphous, hygroscopic powder.
Verwenden
Enzyme inhibitor.
Verwenden
Cilastatin sodium is a dipeptidase inhibitor with nephroprotective effects.
Definition
ChEBI: The monosodium salt of cilastatin. It is an inhibitor of dehydropeptidase I (membrane dipeptidase, 3.4.13.19), an enzyme found in the brush border of renal tubes and responsible for degrading the antibiotic imipenem. Cilastatin sodium is therefore administ red with imipenem to prolong the antibacterial effect of the latter by preventing its renal metabolism to microbiologically inactive and potentially nephrotoxic products.
Allgemeine Beschreibung
Cilastatin sodium salt is off-white to yellowish-white, hygroscopic, amorphous compound. It is derivatized from heptenoic acid. Its molecular mass is 380.43 g.
Biologische Aktivität
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.
Einzelnachweise
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