Vinblastine


Vinblastine
Vinblastine
Systematic (IUPAC) name
dimethyl (2β,3β,4β,5α,12β,19α)- 15-[(5S,9S)- 5-ethyl- 5-hydroxy- 9-(methoxycarbonyl)
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682848
Pregnancy cat. D(AU) D(US)
Legal status POM (UK) -only (US)
Routes Exclusively intravenous
Pharmacokinetic data
Bioavailability n/a
Metabolism Hepatic (CYP3A4-mediated)
Half-life 24.8 hours (terminal)
Excretion Biliary and renal
Identifiers
CAS number 865-21-4 YesY
ATC code L01CA01
PubChem CID 241903
DrugBank APRD00708
ChemSpider 211446 YesY
UNII 5V9KLZ54CY YesY
KEGG D08675 YesY
ChEBI CHEBI:27375 YesY
ChEMBL CHEMBL159 N
Synonyms vincaleukoblastine
Chemical data
Formula C46H58N4O9 
Mol. mass 810.974 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis.

Contents

History

Vinblastine was first isolated by Robert Noble and Charles Thomas Beer from the Madagascar periwinkle plant. Vinblastine's utility as a chemotherapeutic agent was first discovered when it was crushed into a tea. Consumption of the tea led to a decreased number of white blood cells; therefore, it was hypothesized that vinblastine might be effective against cancers of the white blood cells such as lymphoma.

Pharmacology

Vinblastine is a vinca alkaloid and a chemical analogue of vincristine. It binds tubulin, thereby inhibiting the assembly of microtubules. It is M phase cell cycle specific since microtubules are a component of the mitotic spindle and the kinetochore which are necessary for the separation of chromosomes during anaphase of mitosis. Toxicities include bone marrow suppression (which is dose-limiting), gastrointestinal toxicity, potent vesicant (blister-forming) activity, and extravasation injury (forms deep ulcers). Vinblastine paracrystals may be composed of tightly-packed unpolymerized tubulin or microtubules.[1]

Vinblastine is reported to be an effective component of certain chemotherapy regimens, particularly when used with bleomycin, and methotrexate in VBM chemotherapy for Stage IA or IIA Hodgkin lymphomas. The inclusion of vinblastine allows for lower dosese of bleomycin and reduced overall toxicity with larger resting periods between chemotherapy cycles. [2]

Mechanism of Action

Microtubule disruptive drugs like vinblastine, colcemid, nocodazole have been reported to act by two mechanisms.[3] At very low concentrations they suppress microtubule dynamics and at higher concentrations they reduce microtubule polymer mass. Recent findings indicate that they also produce microtubule fragments by stimulating microtubule minus-end detachment from their organizing centers. Dose-response studies further indicate that enhanced microtubule detachment from spindle poles correlate best with cytotoxicity.[4]

Isolation and Synthesis

Vinblastine may be isolated from the Madagascar Periwinkle (Catharanthus roseus), along with several of its precursors- catharanthine and vindoline. Extraction is costly and yields of vinblastine and its precursors are low. Enantioselective synthesis has been of considerable interest in recent years, as the natural mixture of isomers is not an economical source for the required C16’S, C14’R stereochemistry of biologically active vinblastine. Initially, the approach depends upon an enantioselective Sharpless epoxidation, which sets the stereochemistry at C20. The desired configuration around C16 and C14 can then be fixed during the ensuing steps. In this pathway, vinblastine is constructed by a series of cyclization and coupling reactions which create the required stereochemistry. The overall yield may be as great as 22%, which makes this synthetic approach more attractive than extraction from natural sources, whose overall yield is about 10 %. [5] Stereochemistry is controlled through a mixture of chiral agents (Sharpless catalysts), and reaction conditions (temperature, and selected enantiopure starting materials). [6]


Indications

Vinblastine is a component of a number of chemotherapy regimens, including ABVD for Hodgkin lymphoma. It is also used to treat histiocytosis according to the established protocols of the Histiocytosis Association of America.

See also

  • Rosy Periwinkle
  • ABVD

Footnotes

  1. ^ Starling D (1 January 1976). "Two ultrastructurally distinct tubulin paracrystals induced in sea-urchin eggs by vinblastine sulphate.". J Cell Sci 20 (1): 79–89. PMID 942954. http://jcs.biologists.org/cgi/reprint/20/1/79. 
  2. ^ Goppi, P. G.; et al.. "Vinblastine, Bleomycin, and Methotrexate Chemotherapy plus Irradiation for Patients with Early-Stage, Favorable Hodgkin Lymphoma". CANCER. 98 (11): 2393–2401. 
  3. ^ Jordan MA, Leslie W (Apr 4, 2004). "Microtubules as a target for anticancer drugs". Nat Rev Cancer 4 (4): 253–65. doi:10.1038/nrc1317. PMID 15057285. 
  4. ^ Yang H, Ganguly A, Cabral F (Aug 9, 2010). "Inhibition of cell migration and cell division correlate with distinct effects of microtubule inhibiting drugs". J. Biol. Chem. 285 (42): 32242–50. doi:10.1074/jbc.M110.160820. PMC 2952225. PMID 20696757. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2952225. 
  5. ^ Kuehne, M. E.; Matson, P. A.; and Bornmann, W. G. (April 20, 1990). "Enantioselective Syntheses of Vinblastine, Leurosidine, Vincovaline, and 20'-epi –Vincovaline". J. Org. Chem. 56 (2): 513–528. 
  6. ^ Yokoshima, S; Tokuyama, H; and Fukuyama, T.. "Total Synthesis of (+)-Vinblastine: Control of the Stereochemistry at C18′". The Chemical Record. 10: 101–118. 

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Look at other dictionaries:

  • Vinblastine — Général No CAS …   Wikipédia en Français

  • vinblastine — [vin blas′tēn, vin blas′tin] n. an alkaloid, C46H58N4O9·H2SO4, obtained from the leaves of a periwinkle ( Vinca rosea) and used as a drug in the treatment of Hodgkin s disease and other lymphomas: in full vinblastine sulfate …   English World dictionary

  • vinblastine — vinblastine. См. винбластин. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • vinblastine — ● vinblastine nom féminin Alcaloïde indolique extrait de la pervenche rose (Vinca rosea), utilisé pour son action antimitotique, en particulier dans le traitement de la maladie de Hodgkin …   Encyclopédie Universelle

  • vinblastine — noun Etymology: contraction of vincaleukoblastine, from vinca + leukoblast developing leukocyte, from leuk + blast Date: 1962 an alkaloid C46H58N4O9 from the rosy periwinkle used especially in the form of its sulfate to treat human neoplastic… …   New Collegiate Dictionary

  • vinblastine — Alkaloid (818D) isolated from Vinca (periwinkle) : binds to tubulin heterodimer and induces formation of paracrystals rather than tubules. Net result is that microtubules disappear as they disassemble and are not replaced. Used in tumour… …   Dictionary of molecular biology

  • vinblastine — /vin blas teen/, n. Pharm. an alkaloid, C46H58N4O9, derived from the periwinkle Vinca rosea, used in the treatment of various malignant conditions, esp. in the management of lymphomas. [1960 65; < NL Vin(ca) a periwinkle genus + (LEUKO)BLAST +… …   Universalium

  • vinblastine — noun A particular drug used in chemotherapy …   Wiktionary

  • vinblastine — vin·blas·tine ( )vin blas .tēn n an alkaloid that is obtained from the rosy periwinkle and that is used esp. in the form of its sulfate C46H58N4O9·H2SO4 to treat human neoplastic diseases (as Hodgkin s disease and testicular carcinoma) called… …   Medical dictionary

  • vinblastine — vin·blas·tine …   English syllables


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