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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2020-02-26 21:41:47 UTC
HMDB IDHMDB0015535
Secondary Accession Numbers
  • HMDB15535
Metabolite Identification
Common NameCilastatin
DescriptionCilastatin, also known as cilastatin sodium, belongs to the class of organic compounds known as n-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom. Cilastatin is a very strong basic compound (based on its pKa). 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. A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. In case of overdose with the combination product, including and , it is recommended to provide supportive care. Since the antibiotic, , is one such antibiotic that is hydrolyzed by dehydropeptidase, cilastatin is used in combination with imipenem to prevent its metabolism. Cilastatin is an inhibitor of renal dehydropeptidase, an enzyme responsible for both the metabolism of thienamycin beta-lactam antibiotics as well as conversion of leukotriene D4 to leukotriene E4. Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase. Cilastatin is a renal dehydropeptidase-I inhibitor.
Structure
Data?1582753307
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
(L)-7-(2-Amino-2-carboxy-ethylsulfanyl)-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoateGenerator
(L)-7-(2-Amino-2-carboxy-ethylsulphanyl)-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoateGenerator
(L)-7-(2-Amino-2-carboxy-ethylsulphanyl)-2-[(2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoic acidGenerator
(Z)-7-((R)-2-Amino-2-carboxy-ethylsulfanyl)-2-[((S)-2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoateGenerator
(Z)-7-((R)-2-Amino-2-carboxy-ethylsulphanyl)-2-[((S)-2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoateGenerator
(Z)-7-((R)-2-Amino-2-carboxy-ethylsulphanyl)-2-[((S)-2,2-dimethyl-cyclopropanecarbonyl)-amino]-hept-2-enoic acidGenerator
Cilastatin sodiumHMDB
Monosodium salt, cilastatinHMDB
Salt, cilastatin monosodiumHMDB
Cilastatin monosodium saltHMDB
Sodium, cilastatinHMDB
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 KeyDHSUYTOATWAVLW-WFVMDLQDSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as n-acyl-alpha amino acids. N-acyl-alpha amino acids are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids
Alternative Parents
Substituents
  • N-acyl-alpha-amino acid
  • L-cysteine-s-conjugate
  • Cysteine or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Medium-chain fatty acid
  • Cyclopropanecarboxylic acid or derivatives
  • Dicarboxylic acid or derivatives
  • Unsaturated fatty acid
  • Fatty acid
  • Fatty acyl
  • Amino acid
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Dialkylthioether
  • Sulfenyl compound
  • Carboxylic acid
  • Thioether
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Primary aliphatic amine
  • Organic nitrogen compound
  • Organic oxide
  • Carbonyl group
  • Primary amine
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Amine
  • Aliphatic homomonocyclic compound
Molecular FrameworkAliphatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.1 g/LNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.1 g/LALOGPS
logP-0.29ALOGPS
logP-1.3ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)2.53ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area129.72 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity92.85 m³·mol⁻¹ChemAxon
Polarizability38.28 ųChemAxon
Number of Rings1ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0007-9143000000-9267c830716476e05220Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-000j-9634300000-05e8bb2de2e0d6d642d3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0a4i-0009000000-ef2198c6225f95e6b765Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-004i-0092000000-f0483d6314128c99a866Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03fr-0089000000-e23865517b151264287cSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0009000000-f94440db25517ee87789Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-0193000000-9c52bb64f789ddf44d03Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-01t9-0890000000-a16bc40171fdaad5d00fSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-01q9-0900000000-7f6fb4bc2c8d8b74669aSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-001i-0900000000-f7395a558e6db43df825Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0009000000-65b5dae5f837cb16f232Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-0093000000-f41454497f85c6c231e3Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-0890000000-2d4e1ce343461b9c33ffSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-001i-0900000000-f7395a558e6db43df825Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03fr-0079000000-f5a7ea868a31218529fbSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0009000000-afc7a1706de335756516Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0uxr-0292000000-fc9fdc71c26de516aa47Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0f89-0980000000-c7e9f3733dc9d5876f69Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0f89-0940000000-5e461031ed3e8be30dceSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udl-0197000000-ed9524572e0f6a20cf73Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0009000000-92adcd25c03169bce114Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-9350000000-49e92e77b9da299b75c9Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-9100000000-93ce7c9a2d2ddb232af8Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-9100000000-a5fb73965dbd68cad5caSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-9000000000-314ddc83e7521820bbfcSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-9000000000-f4a4b127adc8552d8fffSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0009000000-ee64e7f7019c68d1b37cSpectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01597 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01597 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01597
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4940183
KEGG Compound IDC01675
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkCilastatin
METLIN IDNot Available
PubChem Compound6435415
PDB IDNot Available
ChEBI ID3697
Food Biomarker OntologyNot Available
VMH IDNot Available
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:3474745 ]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:12023506 ]