Vincristine sulfate
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MedKoo CAT#: 100920

CAS#: 2068-78-2

Description: Vincristine sulfate is the sulfate salt of a natural alkaloid isolated from the plant Vinca rosea Linn with antimitotic and antineoplastic activities. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.


Price and Availability

Size
Price

100mg
USD 190
1g
USD 950
Size
Price

200mg
USD 350
2g
USD 1650
Size
Price

500mg
USD 550
5g
USD 2950

Vincristine sulfate purity > 98%, is in stock. The same day shipping out after order is received. Note: the estimated shipping out time for order >1g may be 2 weeks.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 100920
Name: Vincristine sulfate
CAS#: 2068-78-2
Chemical Formula: C46H56N4O10
Exact Mass:
Molecular Weight: 824.96
Elemental Analysis: C, 66.97; H, 6.84; N, 6.79; O, 19.39


Related CAS #: 2068-78-2 (sulfate)   57-22-7 (free)  

Synonym: leurocristine sulfate, Vincasar PFS, Oncovin, VCR

IUPAC/Chemical Name: (3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((3S,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 sulfate.

InChi Key: AQTQHPDCURKLKT-JKDPCDLQSA-N

InChi Code: InChI=1S/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+;/m1./s1

SMILES Code: O=C([C@]1(O)[C@]2([H])N(C=O)C3=C(C=C([C@@]4(C(OC)=O)C[C@@]5([H])C[C@@](O)(CC)C[N@](C5)CCC6=C4NC7=C6C=CC=C7)C(OC)=C3)[C@]2(CCN8CC=C9)[C@]8([H])[C@]9(CC)[C@H]1OC(C)=O)OC.O=S(O)(O)=O


Technical Data

Appearance:
White to off-white, odorless amorphous or crystalline powder

Purity:
>99% (or refer to the Certificate of Analysis)

Safety Data Sheet (MSDS):

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, water, slightly soluble in ethanol.

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

History
Having been used as a folk remedy for centuries, studies in the 1950s revealed that C. 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 lead by Dr. J.G. Armstrong; it was then marketed by Eli Lilly and Company.  From http://en.wikipedia.org/wiki/Vincristine.
Having been used as a folk remedy for centuries, studies in the 1950s revealed that C. 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 lead by Dr. J.G. Armstrong; it was then marketed by Eli Lilly and Company.  From http://en.wikipedia.org/wiki/Vincristine.
   
Applications
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, and in treatment for nephroblastoma (Wilms tumor, a kidney tumor common in children). It is also used to induce remission in ALL with Dexamethasone and L Asparaginase. Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP). It is used in combination with prednisone to treat childhood leukemia.   From http://en.wikipedia.org/wiki/Vincristine.
  From http://en.wikipedia.org/wiki/Vincristine.
 
DRUG DESCRIPTION
VINCASAR PFS® (vincristine sulfate injection, USP) is the salt of an alkaloid obtained from a common flowering herb, the periwinkle plant (Vinca rosea Linn.). Originally known as leurocristine, it has also been referred to as LCR and VCR. Vincristine sulfate is a white to slightly yellow, amorphous powder. It is soluble in methanol, freely soluble in water, but only slightly soluble in 95% ethanol. In 98% ethanol, vincristine sulfate has an ultraviolet spectrum with maxima at 221 nm (e+ 47,100). VINCASAR PFS®, a sterile, preservative-free, single use only solution, is available in 1 mg (1 mg/1 mL) and 2 mg (2 mg/2 mL) vials. Each mL contains vincristine sulfate, 1 mg (1.08 mmoL); mannitol, 100 mg; water for injection, q.s. Acetic acid and sodium acetate have been added for pH control. The pH of VINCASAR PFS ranges from 3.5 to 5.5. This product is a sterile solution for cancer/oncolytic use.
 
CLINICAL PHARMACOLOGY
The mechanisms of action of vincristine sulfate remain under investigation.1 The mechanism of action of vincristine sulfate has been related to the inhibition of microtubule formation in the mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Central-nervous-system leukemia has been reported in patients undergoing otherwise successful therapy with vincristine sulfate. This suggests that vincristine sulfate does not penetrate well into the cerebrospinal fluid. Pharmacokinetic studies in patients with cancer have shown a triphasic serum decay pattern following rapid intravenous injection. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, and 85 hours respectively; however, the range of the terminal half-life in humans is from 19 to 155 hours. The liver is the major excretory organ in humans and animals; about 80% of an injected dose of vincristine sulfate appears in the feces and 10% to 20% can be found in the urine. Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.2 Current principles of cancer chemotherapy involve the simultaneous use of several agents. Generally, each agent used has a unique toxicity and mechanism of action so that therapeutic enhancement occurs without additive toxicity. It is rarely possible to achieve equally good results with single-agent methods of treatment. Thus, vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone-marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy).
 


References

1: Harrison TS, Lyseng-Williamson KA. Vincristine sulfate liposome injection: a guide to its use in refractory or relapsed acute lymphoblastic leukemia. BioDrugs. 2013 Feb;27(1):69-74. doi: 10.1007/s40259-012-0002-5. Review. PubMed PMID: 23329395.

2: Silverman JA, Deitcher SR. Marqibo® (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother Pharmacol. 2013 Mar;71(3):555-64. doi: 10.1007/s00280-012-2042-4. Epub 2012 Dec 5. Review. PubMed PMID: 23212117; PubMed Central PMCID: PMC3579462.

3: Keglevich P, Hazai L, Kalaus G, Szántay C. Modifications on the basic skeletons of vinblastine and vincristine. Molecules. 2012 May 18;17(5):5893-914. doi: 10.3390/molecules17055893. Review. PubMed PMID: 22609781.

4: Moriyama B, Henning SA, Leung J, Falade-Nwulia O, Jarosinski P, Penzak SR, Walsh TJ. Adverse interactions between antifungal azoles and vincristine: review and analysis of cases. Mycoses. 2012 Jul;55(4):290-7. doi: 10.1111/j.1439-0507.2011.02158.x. Epub 2011 Nov 29. Review. PubMed PMID: 22126626; PubMed Central PMCID: PMC3345292.

5: Addo NK, Kamaly-Asl ID, Josan VA, Kelsey AM, Estlin EJ. Preoperative vincristine for an inoperable choroid plexus papilloma: a case discussion and review of the literature. J Neurosurg Pediatr. 2011 Aug;8(2):149-53. doi: 10.3171/2011.5.PEDS1187. Review. PubMed PMID: 21806355.

6: Pongudom S, Chinthammitr Y. Inadvertent intrathecal vincristine administration: report of a fatal case despite cerebrospinal fluid lavage and a review of the literature. J Med Assoc Thai. 2011 Feb;94 Suppl 1:S258-63. Review. PubMed PMID: 21721457.

7: Pana ZD, Roilides E. Risk of azole-enhanced vincristine neurotoxicity in pediatric patients with hematological malignancies: old problem - new dilemma. Pediatr Blood Cancer. 2011 Jul 15;57(1):30-5. doi: 10.1002/pbc.22972. Epub 2011 Jan 24. Review. PubMed PMID: 21265011.

8: Latiff ZA, Kamal NA, Jahendran J, Alias H, Goh BS, Syed Zakaria SZ, Jamal R. Vincristine-induced vocal cord palsy: case report and review of the literature. J Pediatr Hematol Oncol. 2010 Jul;32(5):407-10. doi: 10.1097/MPH.0b013e3181e01584. Review. PubMed PMID: 20505534.

9: Eden T, Pieters R, Richards S; Childhood Acute Lymphoblastic Leukaemia Collaborative Group (CALLCG). Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia - an individual patient data meta-analysis involving 5,659 children. Br J Haematol. 2010 Jun;149(5):722-33. doi: 10.1111/j.1365-2141.2010.08148.x. Epub 2010 Mar 16. Review. PubMed PMID: 20331462.

10: Hennipman B, de Vries E, Bökkerink JP, Ball LM, Veerman AJ. Intrathecal vincristine: 3 fatal cases and a review of the literature. J Pediatr Hematol Oncol. 2009 Nov;31(11):816-9. doi: 10.1097/MPH.0b013e3181b83fba. Review. PubMed PMID: 19801949.