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Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:33:17 UTC
HMDB IDHMDB15535
Secondary Accession NumbersNone
Metabolite Identification
Common NameCilastatin
DescriptionA renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4. [PubChem]
Structure
Thumb
Synonyms
ValueSource
(L)-7-(2-amino-2-Carboxy-ethylsulfanyl)-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoic acidChEBI
(Z)-(S)-6-Carboxy-6-[(S)-2,2-dimethylcyclopropanecarboxamido]hex-5-enyl-L-cysteineChEBI
(Z)-7-((R)-2-amino-2-Carboxy-ethylsulfanyl)-2-[((S)-2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoic acidChEBI
CilastatinaChEBI
CilastatineChEBI
CilastatinumChEBI
Chemical FormulaC16H26N2O5S
Average Molecular Weight358.453
Monoisotopic Molecular Weight358.156242642
IUPAC Name(2Z)-7-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}-2-{[(1S)-2,2-dimethylcyclopropyl]formamido}hept-2-enoic acid
Traditional Namecilastatin
CAS Registry Number82009-34-5
SMILES
N[C@@H](CSCCCC\C=C(/NC(=O)[C@H]1CC1(C)C)C(=O)O)C(=O)O
InChI Identifier
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
InChI KeyInChIKey=DHSUYTOATWAVLW-WFVMDLQDSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-aliphatic-alpha amino acids. These are alpha amino acids carrying a N-acylated aliphatic chain.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-aliphatic-alpha amino acids
Alternative Parents
Substituents
  • N-acyl-aliphatic-alpha amino acid
  • S-alkyl-l-cysteine
  • L-alpha-amino acid
  • Alpha-amino acid
  • Carbocyclic fatty acid
  • Medium-chain fatty acid
  • Amino fatty acid
  • Fatty acyl
  • Fatty acid
  • Unsaturated fatty acid
  • Dicarboxylic acid or derivatives
  • Cyclopropanecarboxylic acid or derivatives
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Dialkylthioether
  • Sulfenyl compound
  • Thioether
  • Enamine
  • Carboxylic acid
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Protease Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.00e-01 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.1 mg/mLALOGPS
logP-0.29ALOGPS
logP-1.3ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)2.53ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area129.72 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity92.85 m3·mol-1ChemAxon
Polarizability38.28 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01597
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01597
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01597
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4940183
KEGG Compound IDC01675
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCilastatin
NuGOwiki LinkHMDB15535
Metagene LinkHMDB15535
METLIN IDNot Available
PubChem Compound6435415
PDB IDNot Available
ChEBI ID3697
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Keynan S, Hooper NM, Felici A, Amicosante G, Turner AJ: The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA. Antimicrob Agents Chemother. 1995 Jul;39(7):1629-31. [7492120 ]

Enzymes

General function:
Involved in metalloexopeptidase activity
Specific function:
Hydrolyzes a wide range of dipeptides. Implicated in the renal metabolism of glutathione and its conjugates. Converts leukotriene D4 to leukotriene E4; it may play an important role in the regulation of leukotriene activity
Gene Name:
DPEP1
Uniprot ID:
P16444
Molecular weight:
45673.5
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Farrell CA, Allegretto NJ, Hitchcock MJ: Cilastatin-sensitive dehydropeptidase I enzymes from three sources all catalyze carbapenem hydrolysis and conversion of leukotriene D4 to leukotriene E4. Arch Biochem Biophys. 1987 Jul;256(1):253-9. [3038022 ]
  4. Kumon H, Nasu Y, Ohmori H, Kodama H, Konishi Y: [Effects of cilastatin sodium, an inhibitor of dehydropeptidase-I, on human urinary peptide excretion. Patients with renal insufficiency]. Jpn J Antibiot. 1987 Sep;40(9):1571-83. [3480361 ]
  5. Lin JH, Chen IW, Ulm EH: Dose-dependent kinetics of cilastatin in laboratory animals. Drug Metab Dispos. 1989 Jul-Aug;17(4):426-32. [2571484 ]
  6. Richerson MA, Ambrose PG, Quintiliani R, Nightingale CH: Formulary review of the carbapenems: comparison of imipenem/cilastatin and meropenem. Conn Med. 1998 Mar;62(3):165-9. [9573653 ]
  7. Hirota T, Nishikawa Y, Tanaka M, Igarashi T, Kitagawa H: Characterization of dehydropeptidase I in the rat lung. Eur J Biochem. 1986 Nov 3;160(3):521-5. [3780719 ]
  8. Hirota T, Nishikawa Y, Komai T, Igarashi T, Kitagawa H: Role of dehydropeptidase-I in the metabolism of glutathione and its conjugates in the rat kidney. Res Commun Chem Pathol Pharmacol. 1987 May;56(2):235-42. [3474745 ]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  10. Keynan S, Hooper NM, Felici A, Amicosante G, Turner AJ: The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA. Antimicrob Agents Chemother. 1995 Jul;39(7):1629-31. [7492120 ]

Transporters

General function:
Involved in ion transmembrane transporter activity
Specific function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido- 3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular weight:
61815.8
References
  1. Takeda M, Narikawa S, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters. Eur J Pharmacol. 2001 May 11;419(2-3):113-20. [11426832 ]
  2. Khamdang S, Takeda M, Shimoda M, Noshiro R, Narikawa S, Huang XL, Enomoto A, Piyachaturawat P, Endou H: Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine. J Pharmacol Sci. 2004 Feb;94(2):197-202. [14978359 ]
General function:
Involved in transmembrane transport
Specific function:
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate
Gene Name:
SLC22A7
Uniprot ID:
Q9Y694
Molecular weight:
60025.0
References
  1. Enomoto A, Takeda M, Shimoda M, Narikawa S, Kobayashi Y, Kobayashi Y, Yamamoto T, Sekine T, Cha SH, Niwa T, Endou H: Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors. J Pharmacol Exp Ther. 2002 Jun;301(3):797-802. [12023506 ]