2068-78-2 Usage
Description
Vincristine sulfate (2068-78-2) arrests cell cycle at G2/M by interfering with mitotic spindle formation. Depolymerizes microtubules and blocks binding of tubulin to microtubule proteins.1,2?Induces apoptosis.3?Vincristine sulfate is a clinically useful cancer chemotherapeutic agent.
Chemical Properties
Crystalline Solid
Originator
Oncovin,Lilly ,US ,1963
Uses
Different sources of media describe the Uses of 2068-78-2 differently. You can refer to the following data:
1. Vincristin sulfate USP (Oncovin) is used to treat acute leukemia in children; lymphocytic leukemia; Hodgkin’s disease; non-Hodgkin’s lymphomas; Wilm’s tumor; neuroblastoma; rhabdomyosarcoma.
2. Vincristine sulfate, is used as an anticancer agent, microtubule disrupter, Induces apoptosis in human lymphoma cells. Other applications include as a cell cycle arresting, apoptotic inducing alkaloid.
3. An antitumor alkaloid isolated from Vinca rosea Linn. An antineoplastic.
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.
Brand name
Oncovin (Lilly); Vincasar (Sicor).
Therapeutic Function
Cancer chemotherapy
General Description
Different sources of media describe the General Description of 2068-78-2 differently. You can refer to the following data:
1. Vincristine sulfate is available as a 1-mg/mL solution in 1-,2-, and 5-mL vials for IV administration in acute leukemiaand as part of a multidrug regime for Hodgkin’s and neuroblastoma, Ewing sarcoma, Wilms tumor, soft tissuesarcoma, testicular cancer, liver cancer, and head and neckcancers. It has also been utilized in treating pediatric cancer.Vincristine is highly protein bound (75%) and may also bindto platelets that contain large amounts of tubulin. Numerousmetabolites have been detected and several have been identified,one of which is the 4-O-desacetyl derivative. The metabolismthat does occur is believed to largely be mediatedby CYP3A. Elimination occurs primarily in the bile with aterminal elimination half-life of 23 to 85 hours. The mostcommonly seen toxicity for vincristine is a dose-limitingneurotoxicity caused by effects on axonal microtubules.Symptoms are variable and include peripheral neuropathy,ataxia, seizure, bone pain, and coma. Constipation is also acommonly seen toxicity, and laxatives may be used prophylactically.Other toxicities include alopecia, skin rash, mildmyelosuppression, secretion of antidiuretic hormone,azospermia, and amenorrhea.
2. An anticancer drug. White to slightly yellow, amorphous or crystalline powder. Sensitive to light. Odorless. pH (0.1% solution) 3.5 - 4.5.
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
Check Digit Verification of cas no
The CAS Registry Mumber 2068-78-2 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,0,6 and 8 respectively; the second part has 2 digits, 7 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 2068-78:
(6*2)+(5*0)+(4*6)+(3*8)+(2*7)+(1*8)=82
82 % 10 = 2
So 2068-78-2 is a valid CAS Registry Number.
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
2068-78-2Relevant articles and documents
Methods and compositions for treating primary and secondary tumors of the central nervous system (CNS)
-
, (2008/06/13)
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
-
, (2008/06/13)
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.
