OXALIPLATIN

PRODUCT IDENTIFICATION
CAS NO. 61825-94-3, 63121-00-6 (SP-4-2 (trans))

OXALIPLATIN

EINECS NO.  
FORMULA C8H12N2O4Pt
MOL WT. 371.25

H.S. CODE

 2934.90.4700

TOXICITY

 Rat LD50 Intraperitoneal: 14300ug/kg
SYNONYMS Oxalatoplatin; Trans-l-diaminocyclohexane oxalatoplatinum;
[(1R,2R)-1,2-cyclohexanediamine-N,N’] [oxalato(2-)-O,O’] platinum; SP-4-2-(1R-trans))- (1,2-cyclo hexanediamine-N,N')- (ethanedioato(2-)-O,O') platinum (II); Oxaliplatinum; trans-l-Diamino cyclohexane oxalatoplatinum; cis-((1R,2R)-1,2-Cyclohexanediamine-N,N')(oxalato (2-)-O,O') platinum; Oxaloplatine; Oxaloplatino; Eloxatin; Elplat;
SMILES C1CC[C@@H]2N[Pt+2]3([O-]C(C([O-]3)=O)=O)N[C@@H]2C1

CLASSIFICATION

 Antineoplastic agent (Alkylating), Platinum-based drug

EXTRA NOTES

 Third generation platinum-based chemotherapy drug

PHYSICAL AND CHEMICAL PROPERTIES

PHYSICAL STATE white crystalline powder
MELTING POINT  
BOILING POINT  
SPECIFIC GRAVITY  
SOLUBILITY IN WATER Soluble (7.9 mg/ml)
pH  
VAPOR DENSITY

 

AUTOIGNITION

 

NFPA RATINGS

  

REFRACTIVE INDEX

 

FLASH POINT  
STABILITY

Stable under ordinary conditions

EXTERNAL LINKS & GENERAL DESCRIPTION

Wikipedia Linking: http://en.wikipedia.org/

Google Scholar Search: http://scholar.google.co.kr/

http://www.ncbi.nlm.nih.gov/
Oxaliplatin, a platinum-based chemotherapeutic agent with a 1,2-diaminocyclohexane (DACH) carrier ligand, has shown in vitro and in vivo efficacy against many tumor cell lines, including some that are resistant to cisplatin and carboplatin. The retention of the bulky DACH ring by activated oxaliplatin is thought to result in the formation of platinum-DNA adducts, which appear to be more effective t blocking DNA replication and are more cytotoxic than adducts formed from cisplatin. Studies by the National Cancer Institute (NCI) have suggested that oxaliplatin has a spectrum of activity different from that of either cisplatin or carboplatin, suggesting that it has different molecular targets and/or mechanisms of resistance. Oxaliplatin has been demonstrated to differ in some mechanisms associated with the development of cisplatin resistance. Compared with cisplatin-conditioned cells, deficiencies in mismatch repair (MMR) and increases in replicative bypass, which appear to contribute to cisplatin resistance, have not been shown to induce a similar resistance to oxaliplatin. A decreased likelihood of resistance development makes oxaliplatin a good candidate for first-line therapy. Studies also demonstrate additive and/or synergistic activity with a number of other compounds, however, suggesting the possible use of oxaliplatin in combination therapies.

http://www.drugbank.ca/
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®.

http://www.sigmaaldrich.com/
...While DNA damage is a key factor in the development and evolution of cancer cells, continued damage is used as part of clinical treatments for cancer, forcing malignant cells into apoptosis or senescence. Many chemotheraputic drugs such as bleomycin, mitomycin, and cisplatin, are effective because they cause further DNA damage in cancer cells that replicate at a faster rate than surrounding tissue. Cellular DNA repair mechanisms are a doubleedged sword; by reducing mutations that may lead to cancer, these processes strive for genomic integrity, but the same mechanisms in malignant cells allow those cells to survive additional DNA damage and continue uncontrolled growth. In order to block this survival mechanism within cancer cells, clinical trials are now being performed using inhibitors to specific DNA repair enzymes, including MGMT, PARP, and DNA-PK.

Local
Carboplatin, a platinum coordination compound which contains a platinum atom surrounded with two ammonia groups and two other ligands in a ring structure. Cisplatin is an analogue which has two chloride atoms instead of ring structure. Oxaliplatin contains a platinum atom complexed with 1,2-diaminocyclohexane and with an oxalate ligand as a leaving group. It is known that diaminocyclohexane group contributes greater cytotoxicity than cisplatin and carboplatin. Oxaliplatin is not generally cross-resistant to cisplatin or carboplatin. They are capable of forming platinum complexes producing inter- and intrastrand DNA crosslinks with neighboring guanine residues, resulting in DNA-mismatch repair (MMR) activity in the cancer cells. Carboplatin has less nephrotoxicity, neurotoxicity, ototoxicity and emetogenesis and more stability than cisplatin. They, platinum-based antineoplastics, have a broad spectrum of antitumor activity in the treatments of carcinomas of ovarian, testicular, bladder, small and non–small cell lung, head and neck carcinoma, and seminoma. They are synergistic with fluorouracil. They are radiation sensitive. The chemical designation of cisplatin is (SP-4-2)-diaminedichloroplatinum (II). It is a yellow crystalline powder; soluble in water and saline; administered intravenously. The chemical designation of carboplatin is (SP-4-2)-diammine [1,1-cyclobutanedicarboxylato (2-)-0, 0']- platinum (II). It is a white crystalline powder; soluble in water; insoluble in ethanol, acetone, and dimethylacetamide; administered intravenously. The chemical designation of oxaliplatin is SP-4-2-(1R-trans))- (1,2-cyclohexanediamine-N,N')- (ethanedioato(2-)-O,O') platinum (II). It is a white crystalline powder; soluble in water; very slightly soluble in methanol; insoluble in ethanol, hexane, benzene and acetone.

SALES SPECIFICATION

APPEARANCE

 white crystalline powder

IDENTIFICATION

Complies Test A,B

ASSAY

98.0 - 102.0% (HPLC)

PLATINUM CONTENT

48.0 - 50.0%

RELATED SUBSTANCE

Complies

WATER

1.0% max

SPECIFIC ROTATION

+73° ~ +78°

pH

5.0 - 7.0

CLARITY

Complies

SILVER

 10ppm max
TRANSPORTATION
PACKING
II
HAZARD CLASS 6.1
UN NO. 2811

GENERAL DESCRIPTION OF ALKYLATING AGENTS AS ANTITUMOR

Alkylating agents are used in cancer chemotherapy by the substitutiopn of alkyl groups for the hydrogen atoms in biological organic compounds present in cells to inhibit tumor growth with mutagenic activity. They cross-links DNA, makes the strands unable to seperate, and induces mutations. They are cell cycle non-specific drugs. Their effects primarily occurs in proliferating tissues which don't have time to mitose DNA repair systems. Classes of alkylating agents for antineoplastic include:
  • Nitrogen mustard
    • Chlorambucil (CAS RN: 305-03-3)
    • Mechlorethamine (CAS RN: 51-75-2)
    • Melphalan (CAS RN:148-82-3)
    • Uracil Mustard (CAS RN: 66-75-1)
    • Cyclophosphamide (CAS RN: 50-18-0)
    • Iphosphamide (CAS RN: 3778-73-2)
  • Nitrosoureas
    • Triethylenemelamine (CAS RN: 51-18-3)
    • Hexamethylmelamine (CAS RN: 645-05-6)
    • Bis-chloroethylnitrosourea (CAS RN: 154-93-8)
    • Chloroethylcyclohexylnitrosourea (CAS RN: 13010-47-4)
    • Streptozotocin (CAS RN: 18883-66-4)
  • Platinum compounds
    • Carboplatin (CAS RN: 41575-94-4)
    • Oxaliplatin (CAS RN: 61825-94-3)
    • Cisplatin (CAS CN: 15663-27-)
    • Tetraplatin (CAS RN: 62816-98-2)
    • (Carboxyphthalato)platinum (CAS RN: 65296-81-3)
  • Alkyl sulfonates
    • Busulfan (CAS RN: 55-98-1)
    • Mannosulfan  (CAS RN: 7518-35-6)
    • Treosulfan (CAS RN: 299-75-2)
  • Aziridines
    • Thiotepa (CAS RN: 52-24-4)
SAFETY INFORMATION

HAZARD OVERVIEW

Causes skin irritation. May cause an allergic skin reaction. Causes serious eye irritation. May cause respiratory irritation. Suspected of causing cancer. Target Organ Effect, Skin sensitiser, Irritant. Target Organs:Liver injury may occur., Kidney, ears, Blood, Peripheral nervous system., Bone marrow, Testes., Female reproductive system.

GHS

 

SIGNAL WORD

Warning

PICTOGRAMS

HAZARD STATEMENTS

H315-H317-H319-H335-H351

P STATEMENTS

P261-P280-P305 + P351 + P33

EC DIRECTIVES

 

HAZARD CODES

Xn

RISK PHRASES

36/37/38-40-42/43

SAFETY PHRASES

26-36