2068-78-2

Basic information

• Product Name: Vincristine sulfate
• Synonyms: VINCRISTINE SULFATE;VINCRISTINE SULFATE, APOCYNACEAE SPECIES;VINCRISTINE SULFATE SALT;VINCRISTINE SULPHATE;VCR;VCR, LEUKOCRISTINE SULFATE;VCR SULFATE;22-oxo-vincaleukoblastinsulfate(1:1)(salt)
• CAS NO: 2068-78-2
• Molecular Formula: C₄₆H₅₆N₄O₁₀*H₂O₄S
• Molecular Weight: 923.04
• EINECS: 218-190-0
• Product Categories: Alkaloids;API;VINCRISTINE SULPHATE;Intermediates & Fine Chemicals;Pharmaceuticals;Additional Affinity PurificationRecombinant Protein Expression and Analysis;Plant Proteomics;Protein Purification;Purification and Detection;V5;API's;Caspases/Apoptosis;Signalling;Chiral Reagents;Heterocycles;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;CLARINEX;Antineoplastic;Anti-cancer & immunity;Inhibitors
• Mol File: 2068-78-2.mol
• Article Data: 3

Chemical Properties

• Melting Point: 300 °C
• Boiling Point: 273-281 °C
• Appearance: white to off-white/lyophilized powder
• Storage Temp.: 2-8°C
• Solubility: methanol: soluble20mg/mL
• Water Solubility: >=1 g/100 mL at 24 ºC
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in distilled water may be stored at -20° for up to 3 months.
• BRN: 3924631
• CAS DataBase Reference: Vincristine sulfate(CAS DataBase Reference)
• NIST Chemistry Reference: Vincristine sulfate(2068-78-2)
• EPA Substance Registry System: Vincristine sulfate(2068-78-2)

Safety Data

• Hazard Codes: T
• Statements: 61-36/37/38-63-23/24/25-68-62-25
• Safety Statements: 22-24/25-53-45-37/39-26-36/37/39-36/37
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: OH6340000
• F: 8-10
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 2068-78-2(Hazardous Substances Data)

Usage

Description

Vincristine sulfate, also known as Vincansulf, is a naturally occurring alkaloid derived from the Madagascar periwinkle plant (Catharanthus roseus). It is a potent chemotherapeutic agent that works by disrupting microtubule formation, leading to cell cycle arrest and apoptosis in cancer cells. Vincristine sulfate is a white to slightly yellow, amorphous or crystalline powder that is sensitive to light and odorless. It is available as a 1-mg/mL solution for intravenous administration and is highly protein-bound (75%).

Uses

Used in Oncology:
Vincristine sulfate is used as an anticancer agent for the treatment of various types of cancer, including acute leukemia in children, lymphocytic leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, Wilm's tumor, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, soft tissue sarcoma, testicular cancer, liver cancer, and head and neck cancers. It is also utilized in pediatric cancer treatment.
Vincristine sulfate is used as a microtubule disrupter for inducing apoptosis in human lymphoma cells. It is an antineoplastic alkaloid that arrests the cell cycle at the G2/M phase by interfering with mitotic spindle formation, depolymerizes microtubules, and blocks the binding of tubulin to microtubule proteins.
Used in Drug Development:
Vincristine sulfate is used as a reference compound in the development of novel drug delivery systems and formulations to improve its efficacy, bioavailability, and therapeutic outcomes. It serves as a benchmark for the evaluation of new anticancer agents and drug delivery technologies.
Toxicity and Side Effects:
The most common toxicity associated with vincristine sulfate is dose-limiting neurotoxicity, which is caused by effects on axonal microtubules. Symptoms of neurotoxicity include peripheral neuropathy, ataxia, seizures, bone pain, and coma. Other side effects include constipation, alopecia, skin rash, mild myelosuppression, secretion of antidiuretic hormone, azospermia, and amenorrhea.
Brand Names:
Vincristine sulfate is marketed under the brand names Oncovin (Lilly) and Vincasar (Sicor).

Originator

Oncovin,Lilly ,US ,1963

Manufacturing Process

The alkaloid mixture from the extraction of Vinca rosea plants (as in vinblastine extraction) was chromatographed to give vincristine which was then converted to the sulfate, according to US Patent 3,205,220. Vincristine may also be prepared in a semisynthetic process starting from vinblastine. Vinblastine or a salt thereof, preferably the sulfate, is oxidized with chromic acid or with one of its salts at a low temperature, the reaction mixture is neutralized or rendered alkaline and the product is separated therefrom by extraction, the extract is evaporated to dryness, the dry residue is optionally formylated, vincristine, and optionally N-demethylvinblastine also, are isolated from the product, and the product(s) are optionally converted into their salts; preferably into the sulfates, according to US Patent 3,899,493.

Therapeutic Function

Cancer chemotherapy

Air & Water Reactions

Very hygroscopic. Water soluble.

Reactivity Profile

Sensitive to hydrolysis, oxidation and heat. Incompatible with strong oxidizing agents. .

Fire Hazard

Flash point data for Vincristine sulfate are not available; however, Vincristine sulfate is probably combustible.

Biological Activity

Anticancer agent; microtubule disrupter. Induces apoptosis in human lymphoma cells.

Clinical Use

Antineoplastic agent

Veterinary Drugs and Treatments

Vincristine is used as an antineoplastic primarily in combination drug protocols in dogs and cats in the treatment of lymphoid and hematopoietic neoplasms. In dogs, it may be used alone in the therapy of transmissible venereal neoplasms. Because vincristine can induce thrombocytosis (at low doses) and has some immunosuppressant activity, it may also be employed in the treatment of immune-mediated thrombocytopenia.

Drug interactions

Potentially hazardous interactions with other drugs Antibacterials: possible increased risk of ventricular arrhythmias with delamanid. Antiepileptics: phenytoin levels may be reduced. Antifungals: metabolism possibly inhibited by itraconazole and posaconazole (increased risk of neurotoxicity). Antimalarials: avoid with piperaquine with artenimol. Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis). Cytotoxics: toxicity possibly increased by asparaginase, crisantaspase and pegasparagase - give at least 3-24 hours before asparaginase, crisantaspase and pegasparagase; increased risk of hepatotoxicity with dactinomycin.

Metabolism

Vincristine is metabolised in the liver by the cytochrome P450 isoenzymes CYP3A4 and CYP3A5 and excreted mainly in the bile; about 70-80% of a dose is found in faeces, as unchanged drug and metabolites (40-50%), while 10-20% appears in the urine.

Purification Methods

The salt is recrystallised from MeOH. It has UV max at 220, 255 and 296nm (log  4.65, 4.21 and 4.18). It is a monoamine oxidase inhibitor and is used in cancer research [Son et al. J Med Chem 33 1845 1990, Horio et al. Proc Natl Acad Sci USA 85 3580 1988].

References

1) Jordan et al. (1998), Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle; Med. Res. Rev., 18 259 2) Lobert et al. (1996), Interaction of vinca alkaloids with tubulin: a comparison of vinblastine, vincristine, and vinorelbine; Biochemistry, 35 6806 3) Wang et al. (1999), The effect of antimicrotubule agents on signal transduction pathways of apoptosis: a review: Cancer Chemother. Pharmacol., 44 355

InChI:InChI=1/C46H56N4O10.H2O4S/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6;1-5(2,3)4/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3;(H2,1,2,3,4)/t28?,37-,38+,39+,42-,43+,44+,45-,46-;/m0./s1

Downstream Products

• 55324-83-9 N-deformyl-4-deacetylvincristine 
• 18172-50-4 N-deformylvincristine 
• 3704-01-6 4-deacetylvincristine 
• 57-22-7 Vincristine 
• 101156-38-1 cyclovincristine 
• 854756-97-1 12'-(3-hydroxyphenylsulfanyl)vincristine 
• 854756-59-5 12'-(2-chlorobenzylsulfanyl)vincristine 

Relevant articles and documents

Methods and compositions for treating primary and secondary tumors of the central nervous system (CNS)

Methods and compositions for the treatment and/or prophylaxis and/or suppression of primary and/or secondary tumors of the central nervous system (brain and spinal cord, eyes) in mammalian subjects are disclosed, wherein an effective dose of a methylol transfer agent such as Taurolidine and/or Taurultam and/or a bioequivalent is administered to a mammalian subject suffering from, or at risk of growth of, tumors of the central nervous system. Furthermore, methods for local application of Taurolidine and/or Taurultam and/or a bioequivalent in solution are disclosed using microdialysis methods, irrigation methods, implantation methods and angiographic methods.

Bis-indole-alkaloid

A process for the preparation of diindolealkaloids, especially new compounds corresponding to vinblastine or leurosine, in which the N-methyl group is replaced by an N--CH2 --OC2 H5 group having antitumor properties. The starting compounds are subjected to oxidation by chromic acid or an alkali metal dichromate at temperatures from -90° C. to -30° C. but preferably below about -45° C. when the new compounds are to be produced, ethanol being present in this case.