143-67-9 Usage
Uses
Used in Anticancer Applications:
Vinblastine sulfate is used as an antineoplastic agent for the treatment of various cancers, including Hodgkin's disease, lymphosarcoma, reticulum cell sarcoma, neuroblastoma, choriocarcinoma, carcinoma of the breast, lung, oral cavity, testis, bladder, acute and chronic leukemia, histiocytosis, and mycosis fungoides. It modulates several oncological signaling pathways, exerting inhibitory effects on tumor growth and progression.
Used in Pharmaceutical Industry:
Vinblastine sulfate is used as a key component in the development of novel drug delivery systems to enhance its applications and efficacy against cancer cells. Various organic and metallic nanoparticles have been employed as carriers for vinblastine sulfate delivery, aiming to improve its delivery, bioavailability, and therapeutic outcomes.
Originator
Velban ,Lilly ,US ,1961
Therapeutic Function
Cancer chemotherapy
Air & Water Reactions
Water soluble..Rapidly hydrolyzes.
Reactivity Profile
Vinblastine sulfate is sensitive to light, hydrolysis, oxidation, and heat. Vinblastine sulfate is very hygroscopic. .
Health Hazard
SYMPTOMS: Symptoms of exposure to Vinblastine sulfate include temporary mental depression, paresthesias, loss of deep-tendon reflexes, headache, convulsions, psychoses; dysfunction of the autonomic nervous system, with marked constipation, paralytic ileus, urinary retention, bilateral pain and tenderness of the parotid glands associated with dryness of the mouth, sinus tachycardia; nausea, vomiting, anorexia, diarrhea; loss of hair, vesicular mucositis of the mouth, and dermatitis.
Biological Activity
Anticancer agent; microtubule disrupter. Induces apoptosis in cultured hepatocytes and human lymphoma cells.
Biochem/physiol Actions
Primary TargetInteraction of tubulin with microtubule-associated proteins, specifically Tau and MAP2
Clinical Use
Vinblastine sulfate is available as a powder in 10-mg vials and as a solution in 10- and 25-mL vials for IV administrationin the treatment of various cancers including Hodgkin’sdisease, lymphocytic lymphoma, histiocytic lymphoma, advancedmycosis fungoides, advanced testicular carcinoma,and Kaposi sarcoma. It has also been used in treating choriocarcinomaand breast cancer when other therapies havefailed.
Side effects
The major toxic effect of vinblastine is a dose-related bone marrow depression. This is more frequent and severe than with the close structural analog, vincristine. Dose-related leukopenia occurs with a nadir of 4 to 10 days and with recovery occurring over another 7 to 14 days. Because of the relatively predictable nadir, it may be possible to administer vinblastine cautiously as often as every 7 to 10 days. Thrombocytopenia typically occurs; however, with standard dosing regimens, serious platelet depressions are infrequent. Erythrocytes are usually only slightly depressed.
Safety Profile
Poison by ingestion,
intraperitoneal, and intravenous routes. An
experimental teratogen. Human systemic
effects by intravenous route: blood
leukopenia and hair changes. Experimental
reproductive effects. Questionable
carcinogen. Human mutation data reported. When heated to decomposition it emits very
toxic fumes of NOx and SOx. See also
VINCALEUKOBLASTINE and
SULFATES.
Veterinary Drugs and Treatments
Vinblastine may be employed in the treatment of lymphomas, carcinomas,
mastocytomas, and splenic tumors in small animals. It is
more effective than vincristine in the treatment of canine mast cell
tumors.
Drug interactions
Potentially hazardous interactions with other drugs
Aldesleukin: avoid concomitant use.
Antibacterials: toxicity increased by erythromycin
- avoid; possible increased risk of ventricular
arrhythmias with delamanid.
Antiepileptics: phenytoin levels may be reduced.
Antifungals: possible increased risk of toxicity with
itraconazole; metabolism possibly inhibited by
posaconazole (increased risk of neurotoxicity).
Antimalarials: avoid with piperaquine with
artenimol.
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Metabolism
Vinblastine is extensively metabolised mainly in
the liver by the CYP3A group of isoenzymes to
desacetylvinblastine, which is more active than the parent
compound. 33% of the drug is slowly excreted in the urine
and 21% in the faeces within 72 hours.
Purification Methods
Crystallise the sulfate from MeOH or EtOH and dry it in vacuo over conc H2SO4. The free base crystallises from EtOH or MeOH m 211-216o (+ 2MeOH .1 H2O) and forms a stable etherate from Et2O with m 201-211o, and [] D +42o (CHCl3), and UV max at 214 and 259nm (log 4.73 and 4.21). The dihydrochloride has m 244-246o(dec)(MeOH). It is a monoamine oxidase B inhibitor and induces microtubule aggregation. It is an antineoplastic drug for Hodgkin’s lymphoma. [Neuss et al. J Am Chem Soc 81 4754 1959, Jong-KeunSon et al. J Med Chem 33 1845 1990, Warfield & Bouck Science 186 1219 1974, Beilstein 26 III/IV 3167.]
Mode of action
Vinblastine binds to tubulin and inhibits microtubule assembly. This inhibition prevents mitotic spindle formation and results in an accumulation of cells in metaphase. Vinblastine is considered cell cycle phase speci c for mitosis; however, the cytotoxic effect probably occurs in S phase and is expressed only in M phase. At high doses, direct effects may be expressed in S and G1 phases. Vinblastine is assumed to have stathmokinetic (cell cycle arrest) effects similar to vincristine.
Check Digit Verification of cas no
The CAS Registry Mumber 143-67-9 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,4 and 3 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 143-67:
(5*1)+(4*4)+(3*3)+(2*6)+(1*7)=49
49 % 10 = 9
So 143-67-9 is a valid CAS Registry Number.
InChI:InChI=1/C46H58N4O9.H2O4S/c1-8-42(54)23-28-24-45(40(52)57-6,36-30(15-19-49(25-28)26-42)29-13-10-11-14-33(29)47-36)32-21-31-34(22-35(32)56-5)48(4)38-44(31)17-20-50-18-12-16-43(9-2,37(44)50)39(59-27(3)51)46(38,55)41(53)58-7;1-5(2,3)4/h10-14,16,21-22,28,37-39,47,54-55H,8-9,15,17-20,23-26H2,1-7H3;(H2,1,2,3,4)/t28?,37-,38+,39+,42-,43+,44+,45-,46-;/m0./s1
143-67-9Relevant articles and documents
Enantioselective synthesis of: Iboga alkaloids and vinblastine via rearrangements of quaternary ammoniums
Zhang, Yun,Xue, Yibin,Li, Gang,Yuan, Haosen,Luo, Tuoping
, p. 5530 - 5536 (2016)
An efficient and novel strategy for the enantioselective syntheses of various iboga alkaloids has been developed. The salient features include a gold-catalyzed oxidation of a terminal alkyne followed by cyclization, a Stevens rearrangement and a tandem sequence that combines the gold-catalyzed oxidation, cyclization and [1,2]-shift. The catharanthine analogs provided by our approach were further converted to the vinca alkaloid vinblastine and its analogs, which confirmed the remarkable sensitivity of the cytotoxicity to the C20′ substituent of vinblastine.
Synthesis of (+)-vinblastine and its analogues
Miyazaki, Tohru,Yokoshima, Satoshi,Simizu, Siro,Osada, Hiroyuki,Tokuyama, Hidetoshi,Fukuyama, Tohru
, p. 4737 - 4740 (2008/03/15)
(Chemical Equation Presented) A synthetic route to vinblastine and its analogues with an ethynyl group, which features a stereoselective coupling of an 11-membered key intermediate with vindoline, is described. Transformations of the alkynyl moiety including a partial reduction as well as a Sonogashira coupling furnished a variety of analogues.
Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers
-
, (2008/06/13)
Methods for reducing or inhibiting the irreversible inactivation of water-soluble biologically active agents in biodegradable polymeric delivery systems which are designed to release such agents over a prolonged period of time, such as PLGA delivery systems are provided. The method comprises preparing a PLGA delivery systems whose microclimate, i.e. the pores where the active agent resides, uniformly or homogenously maintain a pH of between 3 and 9, preferably between 4 and 8, more preferably between 5 and 7.5 during biodegradation. Depending on the size of the delivery system, and the initial bulk permeability of the polymer, this result is achieved by (a) incorporating a water-soluble carrier into the delivery system, (b) incorporating a select basic additive (or antacid) into the delivery system, (c) incorporating both a water soluble carrier and a select basic additive into the delivery system, (d) adding a pore forming molecule for increasing the rate of release of low molecular weight monomers and oligomers into the delivery system, (e) using a PLGA polymer with reduced glycolide content, i.e. PLGA with from 100% to 75% lactide and 0 to 25% glycolide) (f) using a microencapsulation method that yields a more extensive pore-network, e.g. oil-in-oil emulsion-solvent extraction as opposed to water-in-oil-in water-solvent evaporation method, and (g) combinations thereof.
