(3aR,7aR)-octahydro-2',5'-dioxaspiro[cyclohexa[d]1,3-diaza-2-platinacyclopentane-2,1'-cyclopentane]-3',4'-dione

• ChemBase ID: 408
• Molecular Formular: C8H12N2O4Pt
• Molecular Mass: 395.26988
• Monoisotopic Mass: 395.04449787
• SMILES: C1CCC[C@@H]2[C@@H]1N[Pt]1(N2)OC(=O)C(=O)O1
• Canonical SMILES: O=C1O[Pt]2(OC1=O)N[C@H]1[C@H](N2)CCCC1
• InChI: InChI=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
• InChIKey: DWAFYCQODLXJNR-BNTLRKBRSA-L

NAMES AND DATABASE IDS

Names

• IUPAC name: (3aR,7aR)-octahydro-2',5'-dioxaspiro[cyclohexa[d]1,3-diaza-2-platinacyclopentane-2,1'-cyclopentane]-3',4'-dione
• IUPAC Traditional name: (3aR,7aR)-octahydro-2',5'-dioxaspiro[cyclohexa[d]1,3-diaza-2-platinacyclopentane-2,1'-cyclopentane]-3',4'-dione
• Brand Name: Eloxatin
• Synonyms: Oxaloplatino [Spanish]; Oxaloplatine [French]; Oxaliplatinum [Latin]; Oxaliplatino [Spanish]; Oxaliplatin [Usan:Inn:Ban]; oxaliplatin; Oxaliplatin

Database IDs

• CAS Number: 61825-94-3
• PubChem SID: 160963871; 46509083
• PubChem CID: 9887053; 6857599

CALCULATED PROPERTIES

JChem

• H Acceptors: 4
• H Donor: 2
• LogD (pH = 5.5): 1.1968232
• LogD (pH = 7.4): 1.7154633
• Log P: 1.7284
• Molar Refractivity: 65.921 cm^3
• Polarizability: 26.067959 Å^3
• Polar Surface Area: 76.66 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.04
• LOG S: -1.51
• Solubility (Water): 1.24e+01 g/l

DETAILS

DrugBank - DB00526

• Drug Groups: approved; investigational
• Description: Oxaliplatin 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®.
• Indication: Used 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.
• Pharmacology: Oxaliplatin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Oxaliplatin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.
• Toxicity: There have been five cases of oxaliplatin overdose reported. One patient received two 130 mg/m2 doses of oxaliplatin (cumulative dose of 260 mg/m^2) within a 24-hour period. The patient experienced Grade 4 thrombocytopenia (<25,000/mm^3) 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.
• Affected Organisms: Humans and other mammals
• Biotransformation: Oxaliplatin 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.
• Absorption: Bioavailability is complete following intravenous administration.
• Half Life: Approximately 10 - 25 minutes
• Protein Binding: Plasma protein binding of platinum (active metabolite) is irreversible and is greater than 90%.
• 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%.
• Distribution: * 440 L
• References: 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. [Pubmed] ; Graham J, Mushin M, Kirkpatrick P: Oxaliplatin. Nat Rev Drug Discov. 2004 Jan;3(1):11-2. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• 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. Pubmed
• Graham J, Mushin M, Kirkpatrick P: Oxaliplatin. Nat Rev Drug Discov. 2004 Jan;3(1):11-2. Pubmed