Oxaliplatin (T3D2674)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2009-07-15 20:46:41 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2674
Identification
Common NameOxaliplatin
ClassSmall Molecule
DescriptionOxaliplatin is a platinum-based chemotherapy drug in the same family as cisplatin and carboplatin. It is typically administered in combination with fluorouracil and leucovorin in a combination known as Folfox for the treatment of colorectal cancer. Compared to cisplatin the two amine groups are replaced by cyclohexyldiamine for improved antitumour activity. The chlorine ligands are replaced by the oxalato bidentate derived from oxalic acid in order to improve water solubility. Oxaliplatin is marketed by Sanofi-Aventis under the trademark Eloxatin®.
Compound Type
  • Antineoplastic Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Eloxatin
L-OHP
Chemical FormulaC8H12N2O4Pt
Average Molecular Mass395.276 g/mol
Monoisotopic Mass395.044 g/mol
CAS Registry Number61825-94-3
IUPAC Nameplatinum(4+) ion (1R,2R)-cyclohexane-1,2-diaminide oxalate
Traditional Nameplatinum(4+) ion (1R,2R)-cyclohexane-1,2-diaminide oxalate
SMILES[Pt+4].[O-]C(=O)C([O-])=O.[H][C@@]1([NH-])CCCC[C@@]1([H])[NH-]
InChI IdentifierInChI=1S/C6H12N2.C2H2O4.Pt/c7-5-3-1-2-4-6(5)8;3-1(4)2(5)6;/h5-8H,1-4H2;(H,3,4)(H,5,6);/q-2;;+4/p-2/t5-,6-;;/m1../s1
InChI KeyInChIKey=DWAFYCQODLXJNR-BNTLRKBRSA-L
Chemical Taxonomy
Description belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassDicarboxylic acids and derivatives
Direct ParentDicarboxylic acids and derivatives
Alternative Parents
Substituents
  • Dicarboxylic acid or derivatives
  • Organic transition metal salt
  • Carboxylic acid
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic homomonocyclic compound
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceStable, Store cool (MSDS, A308).
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility2.75e+01 g/L
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.6 g/LALOGPS
logP0.19ALOGPS
logP-0.008ChemAxon
logS-2ALOGPS
pKa (Strongest Basic)9.99ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity30.64 m³·mol⁻¹ChemAxon
Polarizability13.08 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureInhalation. Bioavailability is complete following intravenous administration. When a single 2-hour intravenous infusion of oxaliplatin at a dose of 85 mg/m^2 is given, the peak serum concentration was 0.814 mcg/mL.
Mechanism of ToxicityOxaliplatin undergoes nonenzymatic conversion to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. After activation, oxaliplatin binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and transcription. Cytotoxicity is cell-cycle nonspecific.
MetabolismOxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. There is no evidence of cytochrome P450-mediated metabolism in vitro. Route of Elimination: The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of oxaliplatin, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%. Half Life: The decline of ultrafilterable platinum levels following oxaliplatin administartion is triphasic, with two distribution phases: t1/2alpha; 0.43 hours and t1/2beta; 16.8 hours. This is followed by a long terminal elimination phase that lasts 391 hours (t1/2gamma).
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed in combination with infusional 5-FU/LV, is indicated for the treatment of advanced carcinoma of the colon or rectum and for adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor (1).
Minimum Risk LevelNot Available
Health EffectsAnemia, sensory neuropathy such as paresthesia, dysesthesia, laryngospasm and facial muscle spasms, gastrointestinal disorders (1).
SymptomsThere have been five cases of oxaliplatin overdose reported. One patient received two 130 mg/m2 doses of oxaliplatin (cumulative dose of 260 mg/m2) within a 24-hour period. The patient experienced Grade 4 thrombocytopenia (<25,000/mm3) without any bleeding, which resolved. Two other patients were mistakenly administered oxaliplatin instead of carboplatin. One patient received a total oxaliplatin dose of 500 mg and the other received 650 mg. The first patient experienced dyspnea, wheezing, paresthesia, profuse vomiting and chest pain on the day of administration. She developed respiratory failure and severe bradycardia, and subsequently did not respond to resuscitation efforts. The other patient also experienced dyspnea, wheezing, paresthesia, and vomiting. Most common adverse reactions (incidence > 40%) were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue and stomatitis.
TreatmentThere is no known antidote. Patients suspected of receiving an overdose should be monitored, and supportive treatment should be administered. The maximum dose of oxaliplatin that has been administered in a single infusion is 825 mg. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00526
HMDB IDHMDB14667
PubChem Compound ID6857599
ChEMBL IDCHEMBL414804
ChemSpider ID8062727
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID31941
BioCyc IDNot Available
CTD IDNot Available
Stitch IDOxaliplatin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOxaliplatin
References
Synthesis Reference

Masazumi Eriguchi, “Liposome preparations containing oxaliplatin.” U.S. Patent US20040022842, issued February 05, 2004.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Pasetto LM, D'Andrea MR, Rossi E, Monfardini S: Oxaliplatin-related neurotoxicity: how and why? Crit Rev Oncol Hematol. 2006 Aug;59(2):159-68. Epub 2006 Jun 27. [16806962 ]
  3. Graham J, Mushin M, Kirkpatrick P: Oxaliplatin. Nat Rev Drug Discov. 2004 Jan;3(1):11-2. [14756144 ]
  4. FDA label
  5. LC Laboratories (2008). Material Safety Data Sheet: Oxaliplatin. [Link]
  6. Drugs.com [Link]
  7. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. Sharma S, Gong P, Temple B, Bhattacharyya D, Dokholyan NV, Chaney SG: Molecular dynamic simulations of cisplatin- and oxaliplatin-d(GG) intrastand cross-links reveal differences in their conformational dynamics. J Mol Biol. 2007 Nov 9;373(5):1123-40. Epub 2007 Aug 23. [17900616 ]
  4. Zhu G, Chang P, Lippard SJ: Recognition of platinum-DNA damage by poly(ADP-ribose) polymerase-1. Biochemistry. 2010 Jul 27;49(29):6177-83. doi: 10.1021/bi100775t. [20550106 ]
  5. Ramachandran S, Temple BR, Chaney SG, Dokholyan NV: Structural basis for the sequence-dependent effects of platinum-DNA adducts. Nucleic Acids Res. 2009 May;37(8):2434-48. doi: 10.1093/nar/gkp029. Epub 2009 Mar 2. [19255091 ]