Vincristine - wikipedia Vincristine Not to be confused with vinblastine. Vincristine Clinical data Pronunciation / ˈvɪnˈkrɪstiːn / ( listen ) Trade names Oncovin, Vincasar, others AHFS / Drugs.com Monograph MedlinePlus a682822 Pregnancy category AU : D US : D ( Evidence of risk ) Routes of administration intravenous ATC code L01CA02 ( WHO ) Legal status Legal status AU : S4 ( Prescription only ) CA : ℞ - only UK : POM ( Prescription only ) US : ℞ - only Pharmacokinetic data Bioavailability n / a ( not reliably absorbed by the GI tract ) Protein binding ~ 44 % Metabolism Liver, mostly via CYP3A4 and CYP3A5 Biological half - life 19 to 155 hours ( mean : 85 hours ) Excretion Faeces ( 70 -- 80 % ), urine ( 10 -- 20 % ) Identifiers IUPAC name ( 3aR, 3a1R, 4R, 5S, 5aR, 10bR ) - Methyl 4 - acetoxy - 3a - ethyl - 9 - ( ( 5S, 7S, 9S ) - 5 - ethyl - 5 - hydroxy - 9 - ( methoxycarbonyl ) - 2, 4, 5, 6, 7, 8, 9, 10 - octahydro - 1H - 3, 7 - methano ( 1 ) azacycloundecino ( 5, 4 - b ) indol - 9 - yl ) - 6 - formyl - 5 - hydroxy - 8 - methoxy - 3a, 3a1, 4, 5, 5a, 6, 11, 12 - octahydro - 1H - indolizino ( 8, 1 - cd ) carbazole - 5 - carboxylate CAS Number 57 - 22 - 7 PubChem CID 5978 IUPHAR / BPS 6785 DrugBank DB00541 ChemSpider 5758 UNII 5J49Q6B70F KEGG D08679 ChEBI CHEBI : 28445 ChEMBL CHEMBL303560 ECHA InfoCard 100.000. 289 Chemical and physical data Formula Molar mass 824.958 g / mol 3D model ( JSmol ) Interactive image SMILES O = C ( OC ) ( C @ ) 4 ( c2c ( c1ccccc1n2 ) CCN3C ( C @ ) ( O ) ( CC ) C ( C @ @ H ) ( C3 ) C4 ) c5c ( OC ) cc6c ( c5 ) ( C @ @ ) 89 ( C @ @ H ) ( N6C = O ) ( C @ @ ) ( O ) ( C ( = O ) OC ) ( C@H ) ( OC ( = O ) C ) ( C @ @ ) 7 ( / C = C CN ( ( C @ @ H ) 78 ) CC9 ) CC InChI InChI = 1S / C46H56N4O10 / c1 - 7 - 42 ( 55 ) 22 - 28 - 23 - 45 ( 40 ( 53 ) 58 - 5, 36 - 30 ( 14 - 18 - 48 ( 24 - 28 ) Key : OGWKCGZFUXNPDA - XQKSVPLYSA - N ( what is this ? ) ( verify ) Vincristine, also known as leurocristine and marketed under the brandname Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin 's disease, neuroblastoma, and small cell lung cancer among others. It is given intravenously. Most people experience some side effects from vincristine treatment. Commonly it causes a change in sensation, hair loss, constipation, difficulty walking, and headaches. Serious side effects may include neuropathic pain, lung damage, or low blood white cells. It will likely cause harm to the baby if given during pregnancy. It works by stopping cells from dividing properly. Vincristine was first isolated in 1961. It is on the World Health Organization 's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is between 1.80 and 42.60 USD per dose. It is a vinca alkaloid that can be obtained from the Madagascar periwinkle Catharanthus roseus. Contents 1 Medical uses 2 Side effects 3 Mechanism of action 4 Pharmacology 5 History 6 Suppliers 7 Research 8 References 9 External links Medical uses Vincristine is delivered via intravenous infusion for use in various types of chemotherapy regimens. Its main uses are in non-Hodgkin's lymphoma as part of the chemotherapy regimen CHOP, Hodgkin 's lymphoma as part of MOPP, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen in acute lymphoblastic leukemia ( ALL ), and in treatment for nephroblastoma. It is also used to induce remission in ALL with dexamethasone and L - Asparaginase, and in combination with prednisone to treat childhood leukemia. Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura ( TTP ) or chronic idiopathic thrombocytopenic purpura ( ITP ). Side effects The main side effects of vincristine are chemotherapy - induced peripheral neuropathy, hyponatremia, constipation, and hair loss. Chemotherapy - induced peripheral neuropathy can be severe, and may be a reason to reduce or avoid using vincristine. The symptoms of this are progressive and enduring tingling numbness, pain and hypersensitivity to cold, beginning in the hands and feet and sometimes affecting the arms and legs. One of the first symptoms of peripheral neuropathy is foot drop : A person with a family history of foot drop and / or Charcot - Marie - Tooth disease ( CMT ) should avoid the taking of vincristine. Accidental injection of vinca alkaloids into the spinal canal ( intrathecal administration ) is highly dangerous, with a mortality rate approaching 100 percent. The medical literature documents cases of ascending paralysis due to massive encephalopathy and spinal nerve demyelination, accompanied by intractable pain, almost uniformly leading to death. Several patients have survived after aggressive and immediate intervention. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications. Children may do better following this injury. One child, who was aggressively treated at the time of the injection, recovered almost completely with only mild neurological deficits. A significant series of inadvertent intrathecal vincristine administration occurred in China in 2007 when batches of cytarabine and methotrexate ( both often used intrathecally ) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine. The overuse of vincristine may also lead to drug resistance by overexpression of the p - glycoprotein pump ( Pgp ). There is an attempt to overcome resistance by the addition of derivatives and substituents to the vincristine molecule. Mechanism of action Vincristine works partly by binding to the tubulin protein, stopping the cell from separating its chromosomes during the metaphase ; the cell then undergoes apoptosis. The vincristine molecule inhibits leukocyte production and maturation. Pharmacology Vincristine is created through the semi-synthesis coupling of indole alkaloids vindoline and catharanthine in the vinca plant. It can also now be synthesized through a stereocontrolled total synthesis technique which retains the correct stereochemistry at C18 ' and C2 '. The absolute stereochemistry at these carbons is responsible for vincristine 's anticancer activity. The liposome encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the neurotoxicity associated with it. Liposome encapsulation increases vincristine 's plasma concentration and circulation lifetime in the body, and allows the drug to enter cells more easily. History Having been used as a folk remedy for centuries, studies in the 1950s revealed that the rosy periwinkle Catharanthus roseus contained 70 alkaloids, many of which are biologically active. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused myelosuppression ( decreased activity of the bone marrow ) led to its study in mice with leukemia, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skelly - B defatting agent and an acid benzene extract led to a fraction termed `` fraction A ''. This fraction was further treated with aluminium oxide, chromatography, trichloromethane, benz - dichloromethane, and separation by pH to yield vincristine. Vincristine was approved by the United States Food and Drug Administration ( FDA ) in July 1963 as Oncovin. The drug was initially discovered by a team led by Dr. J.G. Armstrong, then marketed by Eli Lilly and Company. Eli Lilly required lots of leaves of the periwinkle plant. They needed one ton of dried leaves to produce one ounce of vincristine. Periwinkle was grown on a ranch in Texas to produce vincristine for some time. Suppliers Three generic drug makers supply vincristine in the United States -- APP, Mayne, and Sicor ( Teva ). Research In 2012 the FDA approved a liposomal formulation of vincristine branded as Marqibo. A nano - particle bound version of vincristine was under development as of 2014. References Jump up ^ `` NCI Drug Dictionary ''. NCI. Archived from the original on 8 December 2015. Retrieved 28 November 2015. Jump up ^ `` Vincristine ''. Dictionary.com. Random House, Inc. Archived from the original on 9 November 2014. Retrieved 9 November 2014. ^ Jump up to : Brayfield, A, ed. ( 13 December 2013 ). `` Vincristine ''. Martindale : The Complete Drug Reference. Pharmaceutical Press. Retrieved 15 April 2014. Jump up ^ `` Oncovin, Vincasar PFS ( vincristine ) dosing, indications, interactions, adverse effects, and more ''. Medscape Reference. WebMD. Archived from the original on 16 April 2014. Retrieved 16 April 2014. ^ Jump up to : `` Vincristine Sulfate ''. The American Society of Health - System Pharmacists. Archived from the original on 2015 - 01 - 02. Retrieved Jan 2, 2015. ^ Jump up to : Ravina, Enrique ( 2011 ). The evolution of drug discovery : from traditional medicines to modern drugs ( 1. Aufl. ed. ). Weinheim : Wiley - VCH. pp. 157 -- 159. ISBN 9783527326693. Archived from the original on 2017 - 08 - 01. Jump up ^ `` WHO Model List of Essential Medicines ( 19th List ) '' ( PDF ). World Health Organization. April 2015. Archived ( PDF ) from the original on 13 December 2016. Retrieved 8 December 2016. Jump up ^ `` Vincristine ''. International Drug Price Indicator Guide. Retrieved 28 November 2015. Jump up ^ del Pino BM. Chemotherapy - induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010 ( archived 2011 - 12 - 11 ) ; 7 ( 4 ) : 6. Jump up ^ Graf, W.D. ; Chance, P.F. ; Lensch, M.W. ; Eng, L.J. ; Lipe, H.P. ; Bird, T.D. ( 1996 ). `` Severe Vincristine Neuropathy in Charcot - Marie - Tooth Disease Type 1A ''. Cancer. 77 ( 7 ) : 1356 -- 1362. PMID 8608515. doi : 10.1002 / ( SICI ) 1097 - 0142 ( 19960401 ) 77 : 7 < 1356 : : AID - CNCR20 > 3.0.CO ; 2 - #. Jump up ^ Qweider, M. ; Gilsbach, J.M. ; Rohde, V. ( 2007 ). `` Inadvertent Intrathecal Vincristine Administration : A Neurosurgical Emergency. Case Report ''. Journal of Neurosurgery : Spine. 6 ( 3 ) : 280 -- 283. PMID 17355029. doi : 10.3171 / spi. 2007.6. 3.280. Jump up ^ Zaragosa, M. ; Ritchey, M. ; Walter, A. ( 1995 ). `` Neurological Consequences of Accidental Intrathecal Vincristine : A Case Report. ''. Medial and Pediatric Oncology. 24 : 61 -- 62. PMID 7968797. doi : 10.1002 / mpo. 2950240114. Jump up ^ Jake Hooker and Walt Bogdanich ( January 31, 2008 ). `` Tainted Drugs Tied to Maker of Abortion Pill ''. New York Times. Archived from the original on March 26, 2017. Jump up ^ Sears, J. ; Boger, D. ( 2015 ). `` Total Synthesis of Vinblastine, Related Natural Products, and Key Analogues and Development of Inspired Methodology Suitable for the Systematic Study of Their Structure - Function Properties ''. Accounts of Chemical Research. 48 : 653 -- 662. doi : 10.1021 / ar500400w. CS1 maint : Multiple names : authors list ( link ) Jump up ^ Jordan, MA ( January 2002 ). `` Mechanism of action of antitumor drugs that interact with microtubules and tubulin. ''. Current medicinal chemistry. Anti-cancer agents. 2 ( 1 ) : 1 -- 17. PMID 12678749. doi : 10.2174 / 1568011023354290. Jump up ^ Silverman, J. ; Deitcher, S. ( 2013 ). `` Marqibo ( R ) ( vincristine sulfate liposome injection ) improves the pharmacokinetics and pharmacodynamics of vincristine ''. Cancer Chemotherapy and Pharmacology. 71 : 555 -- 564. doi : 10.1007 / s00280 - 012 - 2042 - 4. CS1 maint : Multiple names : authors list ( link ) Jump up ^ `` Pharmacognosy of Vinca Alkaloids ''. Archived from the original on 2012 - 01 - 06. Jump up ^ Kuboyama, T. ; Yokoshima, S. ; Tokuyama, H. ; Fukuyama, T. ( 2004 ). `` Stereocontrolled total synthesis of ( + ) - vincristine ''. Proceedings of the National Academy of Sciences of the United States of America. 101 : 11966 -- 11970. doi : 10.1073 / pnas. 0401323101. CS1 maint : Multiple names : authors list ( link ) Jump up ^ Waterhouse, D. ; Madden, T. ; Cullis, P. ; Bally, M. ; Mayer, L. ; Webb, M. ( 2005 ). `` Preparation, Characterization, and Biological Analysis of Liposomal Formulations of Vincristine ''. Methods in Enzymology. 391 : 40 -- 57. CS1 maint : Multiple names : authors list ( link ) Jump up ^ Johnson, I.S. ; Armstrong, J.G. ; Gorman, M. ; Burnett, J.P. ( 1963 ). `` The Vinca Alkaloids : A New Class of Oncolytic Agents '' ( pdf ). Cancer Research. 23 ( 8 Part 1 ) : 1390 -- 1427. PMID 14070392. Jump up ^ `` Eli Lilly engineers developed a life - saving drug from the leaves of the periwinkle plant. -- Treating Diabetes ''. Treating Diabetes. Archived from the original on 8 September 2017. Retrieved 18 June 2017. Jump up ^ FDA press release Aug 9, 2012 Archived 2014 - 11 - 09 at the Wayback Machine. Jump up ^ `` Marqibo label '' ( PDF ). FDA. July 2012. Archived ( PDF ) from the original on 2017 - 02 - 16. Jump up ^ Bind Therapeutics conference call of Nov 6, 2014 Archived 2016 - 03 - 03 at the Wayback Machine. External links Vincristine chemotherapy Vincristine and vinblastine Description and Natural History of the Periwinkle The Boger Route to ( − ) - Vindoline U.S. National Library of Medicine : Drug Information Portal -- Vincristine Intracellular chemotherapeutic agents / antineoplastic agents ( L01 ) SPs / MIs ( M phase ) Block microtubule assembly Vinca alkaloids ( Vinblastine Vincristine Vinflunine Vindesine Vinorelbine ) Block microtubule disassembly Taxanes ( Cabazitaxel Docetaxel Larotaxel Ortataxel Paclitaxel Tesetaxel ) Epothilones ( Ixabepilone ) DNA replication inhibitor DNA precursors / antimetabolites ( S phase ) Folic acid Dihydrofolate reductase inhibitor ( Aminopterin Methotrexate Pemetrexed Pralatrexate ) Thymidylate synthase inhibitor ( Raltitrexed Pemetrexed ) Purine Adenosine deaminase inhibitor ( Pentostatin ) Halogenated / ribonucleotide reductase inhibitors ( Cladribine Clofarabine Fludarabine ) Nelarabine Thiopurine ( Tioguanine Mercaptopurine ) Pyrimidine Thymidylate synthase inhibitor ( Fluorouracil Capecitabine Doxifluridine Tegafur ( + gimeracil / oteracil ) Carmofur Floxuridine ) DNA polymerase inhibitor ( Cytarabine ) Ribonucleotide reductase inhibitor ( Gemcitabine ) Hypomethylating agent ( Azacitidine Decitabine ) Deoxyribonucleotide Ribonucleotide reductase inhibitor ( Hydroxycarbamide ) Topoisomerase inhibitors ( S phase ) Camptotheca ( Camptothecin Cositecan Belotecan Gimatecan Exatecan Irinotecan Lurtotecan Silatecan Topotecan Rubitecan ) II Podophyllum ( Etoposide Teniposide ) II + Intercalation Anthracyclines ( Aclarubicin Daunorubicin Doxorubicin Epirubicin Idarubicin Amrubicin Pirarubicin Valrubicin Zorubicin ) Anthracenediones ( Mitoxantrone Pixantrone ) Crosslinking of DNA ( CCNS ) Alkylating Nitrogen mustards : Mechlorethamine Cyclophosphamide ( Ifosfamide Trofosfamide ) Chlorambucil ( Melphalan Prednimustine ) Bendamustine Estramustine phosphate Uramustine Nitrosoureas : Carmustine Lomustine ( Semustine ) Fotemustine Nimustine Ranimustine Streptozocin Alkyl sulfonates : Busulfan ( Mannosulfan Treosulfan ) Aziridines : Carboquone Thiotepa Triaziquone Triethylenemelamine Platinum - based Carboplatin Cisplatin Dicycloplatin Nedaplatin Oxaliplatin Satraplatin Nonclassical Hydrazines ( Procarbazine ) Triazenes ( Dacarbazine Temozolomide ) Altretamine Mitobronitol Pipobroman Intercalation Streptomyces ( Actinomycin Bleomycin Mitomycins Plicamycin ) Photosensitizers / PDT Aminolevulinic acid / Methyl aminolevulinate Efaproxiral Porphyrin derivatives ( Porfimer sodium Talaporfin Temoporfin Verteporfin ) Other Enzyme inhibitors FI ( Tipifarnib ) CDK inhibitors ( Alvocidib Palbociclib Ribociclib Seliciclib ) PrI Bortezomib Carfilzomib Ixazomib PhI ( Anagrelide ) IMPDI ( Tiazofurin ) LI ( Masoprocol ) PARP inhibitor ( Niraparib Olaparib Rucaparib ) HDAC ( Belinostat Panobinostat Romidepsin Vorinostat ) PIKI ( Idelalisib ) Receptor antagonists ERA ( Atrasentan ) Retinoid X receptor ( Bexarotene ) Sex steroid ( Testolactone ) Other / ungrouped Amsacrine Trabectedin Retinoids ( Alitretinoin Tretinoin ) Arsenic trioxide Asparagine depleters ( Asparaginase / Pegaspargase ) Celecoxib Demecolcine Elesclomol Elsamitrucin Etoglucid Lonidamine Lucanthone Mitoguazone Mitotane Oblimersen Omacetaxine mepesuccinate Eribulin WHO - EM Withdrawn from market Clinical trials : Phase III Never to phase III Retrieved from `` https://en.wikipedia.org/w/index.php?title=Vincristine&oldid=800495669 '' Categories : Vinca alkaloids Commercialization of traditional medicines Eli Lilly and Company Mitotic inhibitors Acetate esters World Health Organization essential medicines Hidden categories : CS1 maint : Multiple names : authors list Webarchive template wayback links Articles with hAudio microformats Articles including recorded pronunciations ( English ) Template : drugs.com link with non-standard subpage Articles with changed EBI identifier ECHA InfoCard ID from Wikidata Articles with changed InChI identifier Drugboxes which contain changes to verified fields Drugboxes which contain changes to watched fields RTT Talk Contents About Wikipedia Català Deutsch Español فارسی Français Italiano Magyar Nederlands 日本 語 ଓଡ଼ିଆ Polski Português Русский Slovenščina Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska Tagalog தமிழ் Українська 中文 Edit links This page was last edited on 13 September 2017, at 22 : 28. 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Question: vincristine acts on which phase of cell cycle
Answer: metaphase