Vincristine

Catalog No.S1241

Vincristine is an inhibitor of polymerization of microtubules by binding to tubulin with IC50 of 32 μM in a cell-free assay.

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Vincristine Chemical Structure

Vincristine Chemical Structure
Molecular Weight: 923.04

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Product Information

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Product Description

Biological Activity

Description Vincristine is an inhibitor of polymerization of microtubules by binding to tubulin with IC50 of 32 μM in a cell-free assay.
Targets Microtubules [1]
(Cell-free assay)
IC50 32 μM
In vitro Vincristine inhibits net addition of tubulin dimers at assembly ends of steady-state microtubules with Ki of 85 nM. [1] At low concentrations, Vincristine stabilizes the spindle apparatus resulting in failure of the chromosomes to segregate leading to metaphase arrest and inhibition of mitosis. At higher concentrations, Vincristine may disrupt and induce total depolymerization of microtubules. [2] Vincristine induces apoptosis in tumor cells and inhibits SH-SY5Y cell proliferation with IC50 of 0.1 μM. Vincristine induces mitotic arrest and promots the expression of caspase-3 and -9 and cyclin B, while decreasing the expression of cyclin D. [4] Vincristine induced neurotoxicity is caused by interference with microtubule function, which results in blockage of axonal transport and thus in axonal degeneration. [5]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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A549MnvPSpVv[3Srb36gRZN{[Xl?MmPINVAxKG6PMX:xOkBpM4\oUGROW09?NGXw[2Rt\WGmczD0c{BiKGyxc4Ogc4YhdWmlcn;0eYJ2dGW|NXn3UWVTOjN3OUiyO|Y>
SGC7901M2nXXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXHJR|UxRTFwMkdihKnDueLCiUCuNVEh|rypL33sMWWyN|U3PDR6Mh?=
SGC7901/LV-NCM1e4cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFi4XW9KSzVyPUGuO|fjiIoEsfMAjVAvOTZizsznM41tNVntVWoyOjN3NkS0PFI>
SGC7901/LV-SGO1MoC3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MnjhTWM2OD12LkO25qCKyrIkgJmwMlM4KM7:Zz;tcC=>M{jTUlI{PTZ2NEiy
SGC7901/VCRNXz1SnUxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Ml3XTWM2Oz1{MD61N-KBkcLz4pEJNU46PiEQvHevcYw>NEPDZ4MzOzV4NES4Ni=>
SGC7901/VCR-NCM2\GSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVviNGZkUUN3ME2xPU45PuLCidMx5qCKOi5yMTFOwIcwdWx?NYfkOYIzOjN3NkS0PFI>
SGC7901/VCR-si-SGO1MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NUHHUG55UUN3ME22MlE56oDLwsJihKkyNjB|IN88[{9udA>?MmTnNlM2PjR2OEK=
SGC7901/ADRM17Me2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M4eyS2lEPTB;Nz64OgKBkcLz4pEJNE43PCEQvHevcYw>MXqyN|U3PDR6Mh?=
SGC7901/ADR-NCM{HKVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M2rlO2lEPTB;OD65N-KBkcLz4pEJNE43QCEQvHevcYw>MX:yN|U3PDR6Mh?=
SGC7901/ADR-si-SGO1NGnY[JNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{HmWGlEPTB;Mz60OwKBkcLz4pEJNE4zQSEQvHevcYw>M{njVFI{PTZ2NEiy
SH-SY5Y M33VNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYiwMlAxOS1zMDFOwG0>NVrwSY5KOjRiaB?=NUDPcIl1UUN3ME2wMlEyO8LzMD6wNVIh|ryPMXKyN|EzQTB4NR?=
SH-SY5Y M1L0N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHWwVYgxNjByMT2xNEDPxE1?Mn7TOFghcA>?NGrKZ3lKSzVyPUCuNFc5yrFyLkCwPUDPxE1?NVq2SG5NOjNzMkmwOlU>
SH-SY5Y NVzmcINbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MleyNE4xODFvMUCg{txOMXK3NkBpMVTJR|UxRTBwMEWxxtExNjByODFOwG0>NEHsUoszOzF{OUC2OS=>
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... Click to View More Cell Line Experimental Data

In vivo Vincristine (3 mg/kg) administrated by a single i.p. injection to mice bearing bilateral subcutaneous xenografts Rh12 or Rh18, induces mean growth delay of >120 and >52 day, and repopulating fractions of 0.06% and 5%, respectively. [6] Vincristine acts on subcutaneous colon 38 tumors in mice by host cell-mediated vascular effects as well as by direct tubulin-mediated cytotoxicity. Vincristine (5 mg/kg) reduces tumor blood flow of tumors by nearly 75% . [7]
Features

Protocol(Only for Reference)

Cell Assay: [1]

Cell lines B16 melanoma cell
Concentrations 10 nM
Incubation Time 3 days
Method Cells are plated in 2 mL of medium in 35-mm plates at a concentration of about 5 × 104 cells/mL and grow for 24 h at 37 ℃ in an atmosphere of 5% CO2 and 95% air. Then medium is replaced with fresh medium lacking or containing 4 nM drug and proliferation is continued for 3 days. Cell counts are done each day in a Coulter Counter after detaching the cells with trypsin and EDTA.

Animal Study: [6]

Animal Models Human rhabdomyosarcoma xenografts Rh12
Formulation Water solutioin
Dosages 3 mg/kg
Administration A single i.p. administration

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Jordan MA, et al. Cancer Res, 1985, 45(6), 2741-2747.

[2] Gidding CE. Crit Rev Oncol Hematol, 1999, 29(3), 267-287.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-05-07)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02724579 Not yet recruiting Untreated Childhood Medulloblastoma Childrens Oncology Group|National Cancer Institute (NCI) October 2016 Phase 2
NCT02538926 Not yet recruiting B Acute Lymphoblastic Leukemia|B Lymphoblastic Lymphoma|Recurrent Adult Acute Lymphoblastic Leukemia|Recurrent B Lymphoblastic Lymphoma|Recurrent T  ...more B Acute Lymphoblastic Leukemia|B Lymphoblastic Lymphoma|Recurrent Adult Acute Lymphoblastic Leukemia|Recurrent B Lymphoblastic Lymphoma|Recurrent T Lymphoblastic Leukemia/Lymphoma|Refractory B Lymphoblastic Lymphoma|Refractory T Lymphoblastic Lymphoma|T Acute Lymphoblastic Leukemia|T Lymphoblastic Lymphoma University of Washington|National Cancer Institute (NCI) August 2016 Phase 2
NCT02723994 Not yet recruiting B-cell Acute Lymphoblastic Leukemia Incyte Corporation|Childrens Oncology Group August 2016 Phase 2
NCT02732015 Not yet recruiting Sarcoma M.D. Anderson Cancer Center|Tesaro, Inc. July 2016 Phase 2
NCT02703272 Not yet recruiting Lymphoma, Non-Hodgkin Janssen Research & Development, LLC June 2016 Phase 3

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Chemical Information

Download Vincristine SDF
Molecular Weight (MW) 923.04
Formula

C46H58N4O14S

CAS No. 2068-78-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms Leurocristine
Solubility (25°C) * In vitro DMSO 100 mg/mL (108.33 mM)
Water 60 mg/mL (65.0 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo Saline 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name  22-​oxo-vincaleukoblastine, sulfate (1:1)

Customer Product Validation (2)


Click to enlarge
Rating
Source Cancer Research, 2013, 73(20): 6310-22 . Vincristine purchased from Selleck
Method [methyl-3H]thymidine Assays
Cell Lines Patched mutant tumor cells
Concentrations 0-10 mmol/L
Incubation Time 48 h
Results Addition of BI-2536 dramatically increased the sensitivity of the tumor cells to vincristine; while the IC50 value for vincristine alone was approximately 5 nMol/L, the IC50 value for vincristine combined with BI-2536 was approximately 0.1 nMol/L.

Click to enlarge
Rating
Source Int J Mol Sci 2012 13, 10736-10749 . Vincristine purchased from Selleck
Method Cell Viability Assay
Cell Lines HXO-RB44 cells
Concentrations 0.1-100 nM
Incubation Time 96 h
Results Compared with the treatment with SG600 or VCR alone, the survival rates of RB cells decreased markedly when treated with the combination of SG600 and VCR in the process with increasing dose. Cytotoxicity of VCR in the HXO-RB44 cell line was also evaluated by IC50 values (Figure B).

Tech Support

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