Carboplatin CAS 41575-94-4
Introduction：Basic information about Carboplatin CAS 41575-94-4, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Carboplatin Basic informationDescription Uses Mechanism of action
| Product Name: | Carboplatin |
| Synonyms: | PARAPLATIN;1,1-cyclobutanedicarboxylatediammineplatinum(ii);1-cyclobutanedicarboxylato(2-)-o,o’)-diammine((sp-4-2)-platinu;1-cyclobutanedicarboxylato)diammine-(cis-platinum(ii;DIAMMINE(1,1-CYCLOBUTANEDICARBOXYLATO)PLATINUM(II);CARBOPLATIN;CARBOPLATINUM;CIS-DIAMINE(1,1-CYCLOBUTANEDICARBOXYLATO)PLATINUM |
| CAS: | 41575-94-4 |
| MF: | C6H12N2O4Pt |
| MW: | 371.25 |
| EINECS: | 255-446-0 |
| Product Categories: | API;Inhibitors;Anti cancer;Anti can;NEMAZINE;metal-ammine complexes;anti-cancer;Antitumors for Research and Experimental Use;Biochemistry;Classes of Metal Compounds;Cyclobutanes & Cyclobutenes;Pt (Platinum) Compounds;Simple 4-Membered Ring Compounds;Transition Metal Compounds;Intermediates & Fine Chemicals;Pharmaceuticals;Active Pharmaceutical Ingredients;Pharmaceutical material and intermeidates |
| Mol File: | 41575-94-4.mol |
Carboplatin Chemical Properties
| Melting point | 228-230°C |
| storage temp. | 2-8°C |
| solubility | Sparingly soluble in water, very slightly soluble in acetone and in ethanol (96 per cent). |
| form | crystal |
| color | white |
| Water Solubility | Soluble in water. |
| Merck | 14,1822 |
| Stability: | Stable. Incompatible with strong oxidizing agents. |
| InChI | InChI=1S/C6H8O4.2H3N.Pt/c7-4(8)6(5(9)10)2-1-3-6;;;/h1-3H2,(H,7,8)(H,9,10);2*1H3;/q;;;+2/p-2 |
| InChIKey | OLESAACUTLOWQZ-UHFFFAOYSA-L |
| SMILES | C12(CCC1)C(=O)O[Pt]OC2=O.N.N |
| EPA Substance Registry System | Carboplatin (41575-94-4) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 46-61-20/21/22-42/43-20/21 |
| Safety Statements | 53-22-26-36/37/39-45 |
| RIDADR | 2811 |
| WGK Germany | 3 |
| RTECS | TP2300000 |
| HS Code | 28439000 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 4 Dermal Acute Tox. 4 Inhalation Acute Tox. 4 Oral Muta. 1B Repr. 1B Resp. Sens. 1 Skin Sens. 1 |
| Hazardous Substances Data | 41575-94-4(Hazardous Substances Data) |
| Toxicity | LD50 in mice (mg/kg): 150 i.p., 140 i.v.; in rats (mg/kg): 85 i.v. (Lelieveld) |
| Description | Carboplatin (Brand name: Paraplatin) is a kind of chemotherapy medication used for the treatment of a series of cancers. It can be used for the treatment of various kinds of cancers including ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. Moreover, it may also be used for treating some types of testicular cancer. Carboplatin belongs to a kind of alkylating agent. It takes effect through three major mechanisms: (1) Attach the alkyl groups to the DNA bases, further causing DNA fragmentation so that DNA replication is inhibited; (2) Cause DNA damage through inducing the formation of cross-links which prevents DNA from being separated for synthesis or transcription; (3) Induce mispairing of the nucleotides leading to mutations. |
| Uses | Carboplatin is a second-generation platinum compound analog with established activity against a broad spectrum of solid tumors including brain tumors, neuroblastoma, rhabdomyosarcoma, and germ cell tumors. It is commonly used for pediatric cancer and approximately one-third of children with solid tumor are estimated to receive carboplatin at some point during their treatment. |
| Mechanism of action | Once carboplatin penetrates the cell membrane, carboplatin is subjected to hydrolysis becoming positively charged. The hydrolyzed product is capable of reacting with any nucleophile, such as the sulfhydryl groups on proteins and nitrogen donor atoms on nucleic acids. Carboplatin connects to the N7 reactive center on purine bases, which elicits DNA injury that blocks replicative machinery and directs cancer cells towards apoptosis. The spectrum of chemical changes induced by carboplatin within DNA is wide, however, the most prominent is the formation of the 1,2-intrastrand [d(GpG)and d(ApG)] adducts of purines. |
| Description | Carboplatin is a second generation, platinum-containing antineoplastic agent with significantly reduced nephro-, neuro-, and ototoxicity in comparison to cisplatin. It is effective in the treatment of advanced ovarian carcinoma of epithelial origin and small cell carcinoma of the lung. |
| Chemical Properties | White Crystals |
| Originator | Johnson Matthey (United Kingdom) |
| Uses | antitumor agent, |
| Uses | Data on carboplatin production have not been found.Carboplatin is used in chemotherapy to treat cancer, andmore particularly to treat cancer of ovary, embryonal carcinomaof the testis, microcellular carcinoma of the lung,neuroblastoma, and squamous cell carcinomas of the headand neck. |
| Uses | Analog of Cisplatin with reduced nephrotoxicity. Antineoplastic |
| Indications | Carboplatin (Paraplatin) is an analogue of cisplatin. Itsplasma half-life is 3 to 5 hours, and it has no significantprotein binding. Renal excretion is the major route ofdrug elimination. Despite its lower chemical reactivity, carboplatinhas antitumor activity that is similar to that of cisplatinagainst ovarian carcinomas, small cell lung cancers,and germ cell cancers of the testis. Most tumors thatare resistant to cisplatin are cross-resistant to carboplatin. The major advantage of carboplatin over cisplatin isa markedly reduced risk of toxicity to the kidneys, peripheralnerves, and hearing; additionally, it producesless nausea and vomiting. It is, however, more myelosuppressivethan cisplatin. Other adverse effects includeanemia, abnormal liver function tests, and occasional allergicreactions. |
| Manufacturing Process | cis-Diammine platinum diiodide was reacted with silver sulfate to give cis-diaquodiammine platinum sulfate. This was reacted with the barium salt of1,1-cyclobutanedicarboxylic acid to yield Carboplatin. |
| Brand name | Paraplatin (Bristol-Myers Squibb). |
| Therapeutic Function | Antitumor |
| General Description | Carboplatin is available in 50-, 150-, and 450-mg vials for IVadministration in the treatment of ovarian cancer, bladdercancer, germ cell tumors, head and neck cancers, small celllung cancer, and NSCLC. Activation of the agent occurs byaquation in a manner similar to that seen for cisplatin. Thepresence of the chelating 1,1-cyclobutane-dicarboxylateslows this reaction 100-fold and reduces the toxicity of theagent. The sites of alkylation and mechanisms of resistanceare like those seen for cisplatin, and the two agents showcross-resistance. The agent is widely distributed upon IV administration but, because of its greater stability, it bindsslowly to plasma proteins, requiring 24 hours to reach 90%bound drug compared with 4 hours for cisplatin. The agent iseliminated in the urine with a terminal elimination half-lifeof 2 to 6 hours. Adverse effects include myelosuppression,which is dose limiting. Other adverse effects include renaltoxicity, nausea, vomiting, and peripheral neuropathy, butthese occur much less frequently than with cisplatin. |
| Pharmaceutical Applications | Carboplatin, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), is a second-generation platinum drug.Its structure is based on cisplatin with the difference that the chloride ligands are exchanged for a bidentatechelating ligand. A consequence is that carboplatin is less reactive than cisplatin and therefore is less nephrotoxicand orthotoxic than the parent compound. Unfortunately, it is more myelosuppressive than cisplatin,which reduces the patients’ white blood cell count and makes them susceptible to infections. Carboplatinwas licensed by the FDA in 1989 under the brand name Paraplatin and has since then gained worldwiderecognition. Carboplatin on its own or in combination with other anticancer agents is used in the treatmentof a variety of cancer types including head and neck, ovarian, small-cell lung, testicular cancer and others. Carboplatin is a pale-white solid showing good aqueous solubility. The synthesis starts with potassiumtetrachloroplatinate, which is reacted to the orange [PtI4]2- anion. |
| Biological Activity | Antitumor agent that forms platinum-DNA adducts. Causes intra- and interstrand DNA crosslinks blocking DNA replication and transcription. Enhances radiation-induced single-strand DNA breakage and displays lower nephrotoxicity than analog cisplatin (cis-Diaminodichloroplatinum ). |
| Biochem/physiol Actions | Carboplatin is a platinum-based antineoplastic drug that damages DNA by forming intrastrand cross-links with neighboring guanine residues. Tumors acquire resistance to these drugs through the loss of DNA-mismatch repair (MMR) activity and the resultant decrease in the induction of programmed cell death. |
| Mechanism of action | Carboplatin, another square planar Pt(II) complex, forms the same cytotoxic hydrated intermediate as cisplatin but does so at a slower rate, making it a less potent chemotherapeutic agent. |
| Clinical Use | This drug induces fewer nonhematological toxicities (e.g., emesis, nephrotoxicity, and ototoxicity) compared to cisplatin, and it is approved for use only in the treatment of ovarian cancer. Unlabeled uses include combination therapy in lung, testicular, and head and neck cancers. |
| Side effects | The ultimate damage done to cells as a result of carboplatin use, however, approaches that of cisplatin. The plasma half-life of carboplatin is 3 hours, and the drug is less extensively bound to serum proteins. Excretion is predominantly renal, and doses must be reduced in patients with kidney disease. Suppression of platelets and white blood cells is the most significant toxic reaction of carboplatin use. |
| Synthesis | Carboplatin, cis-diamino-(1,1-cyclobutandicarboxylate)platinum(II), ismade from cisplatin by reacting it with a solution of silver nitrate, and then with cyclobutan-1,1-dicarboxylic acid to form the desired carboplatin (30.2.5.2). |
| Veterinary Drugs and Treatments | Like cisplatin, carboplatin may be useful in a variety of veterinaryneoplastic diseasesincluding squamous cell carcinomas, ovariancarcinomas, mediastinal carcinomas, pleural adenocarcinomas,nasal carcinomas and thyroid adenocarcinomas. Carboplatin’s primaryuse currently in small animal medicine is in the adjunctivetreatment (post amputation) of osteogenic sarcomas. Its effectivenessin treating transitional cell carcinoma of the bladder has beendisappointing; however, carboplatin may have more efficacy againstmelanomas than does cisplatin. Carboplatin, unlike cisplatin, appears to be relatively safe to usein cats. Carboplatin may be considered for intralesional use in conditionssuch as equine sarcoids or in treating adenocarcinoma inbirds. Whether carboplatin is more efficacious than cisplatin for certaincancers does not appear to be decidedat this point, but thedrug does appear to have fewer adverse effects (less renal toxicityand reducedvomiting) in dogs. |
| Drug interactions | Potentially hazardous interactions with other drugs Antibacterials: increased risk of nephrotoxicity and possibly ototoxicity with aminoglycosides, capreomycin, polymyxins or vancomycin. Antipsychotics: avoid with clozapine, increased risk of agranulocytosis. |
| Metabolism | There is little, if any, true metabolism of carboplatin. Excretion is primarily by glomerular filtration in the urine, with 70% of the drug excreted within 24 hours, most of it in the first 6 hours. Approximately 32% of the dose is excreted unchanged.Platinum from carboplatin slowly becomes protein bound, and is subsequently excreted with a terminal halflife of 5 days or more. |
| storage | +4°C |
| references | [1]. banerji u, sain n, sharp sy, et al. an in vitro and in vivo study of the combination of the heat shock protein inhibitor 17-allylamino-17-demethoxygeldanamycin and carboplatin in human ovarian cancer models. cancer chemother pharmacol, 2008, 62(5): 769-778. [2]. fiebiger w, olszewski u, ulsperger e, et al. in vitro cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines. clin transl oncol, 2011, 13(1): 43-49. [3]. smith ie, evans bd. carboplatin (jm8) as a single agent and in combination in the treatment of small cell lung cancer. cancer treat rev, 1985, 12 suppl a: 73-75. |
Carboplatin Preparation Products And Raw materials
| Raw materials | Ethanol-->Potassium iodide-->Barium hydroxide-->Hydrazine monohydrochloride-->Barium hydroxide octahydrate-->1,1-Cyclobutanedicarboxylic acid-->Silver sulfate-->Potassium chloroplatinate |
