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Leadscope Id LS-228
CAS 57-22-7
DrugBank APRD00495
ChemSpider 5758
Pathway DBs
KEGG D08679
Assay DBs
PubChem CID 5978
ChEMBL 303560
Omics DBs
ToxCast Accepted no
Toxic Effect Apoptosis
ToxBank Accepted no
Target tubulin

Executive Summary

Summary Information

The table listed below contains a summarized listing of toxic effect information leveraged from the 6th European Framework Programme project LIINTOP. For a complete listing of the Gold Compound evaluation criteria please see the Gold Compound Evaluation and Comments immediately following the summary table below.

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




Supplier Sigma Aldrich
Summary Hepatotoxic Effects from the LIINTOP FP6 Program
Hepatocellular necrosis.gif Apoptosis.gif Transporter inhibition.gif Cholestatic.gif Steatotic.gif Phospholipidosis.gif Hepatocyte function.gif Mithochondria impairment.gif Oxidative stress.gif DNA synthesis genotoxicity.gif Covalent binding.gif Idiosyncrasia metabolic.gif Idiosyncrasia immune.gif Bioactivation required.gif LIINTOP severity.gif References

[1] [2] [3] [4] [5]

Gold Compound Evaluation and Comments

The following table is organized into four main sections and provides a detailed assessment by the Gold Compound Working Group for the use of this compound as a standard hepatotoxin. The table's four sections (collapsed by default but will expand when the "show" link is clicked) contains detailed information for the core set of SEURAT compound acceptance criteria.

Standard to Meet Compound Assessment
Criteria Notes
The in vivo therapeutic window is used to estimate an appropriate concentration for in vitro toxicity assays. This in vitro concentration should also be consistent with the exposure implied by pharmacokinetics parameters.
We prefer compounds that require metabolic activation, although standards that are active in themselves will be accepted if they have otherwise valuable properties. We require knowing the active metabolite, and we prefer compounds where the metabolite is stable and can be independently tested in order to verify the mechanism of toxicity as well as of metabolic activation in the test cell line.
Literature data for at least one, but not necessarily all, of the ‘omics datasets is desired. This requirement can be waived in special cases.
The IC50’s for in vitro efficacy and toxicity should be consistent with the therapeutic ratio observed in the clinic. These parameters will be dependent on specific cell type and culture conditions, but differences of more than 30-fold in the in vitro vs. in vivo therapeutic ratios should be considered suspect and carefully justified.
This is not a requirement, but compounds utilized in the EPA testing program can be assumed to have physical properties verified to be suitable for in vitro cellular assays.
Sparing soluble compounds may be assayed for solubility in serum and the percent serum used specified here.
This property will be measured when a sample of compound becomes available.

Proprietary Toxicity Literature Report

Currently Unavailable

Human Adverse Events

The following data table has been mined from the Adverse Events Reporting System (AERS) of the US FDA. Significant human liver events. The first column ("# Reports") is the number of reports found for the corresponding adverse event reported in the third column ("Adverse Event"). The second column ("Report:Baseline Ratio") is ratio calculated from the number of reports ("# Reports") divided by a calculated expected statistical baseline number of reports.

# Reports Report:Baseline Ratio Adverse Event
2 4.75867 adenoviral hepatitis
1 8.64492 bile duct necrosis
1 9.09991 biliary fistula
1 6.56576 hepatitis infectious
27 9.73229 venoocclusive liver disease

FDA and Label Information

The following link will display all of the currently approved FDA drug products on the market. The web page will contain a table listing all current products by their respective Tradenames and primary active ingredients. The list is navigable by simply clicking on the product of interest, which will in turn list all of the NDA's and ANDA's associated with that product. From here users can click on a specific NDA or ANDA and see documents that have been submitted for the product that the FDA has made available via their website. The types of documents include approval history, letters, reviews and labels.
FDA Approved Products

This next url will perform a search in the FDA's system for all labels for products that contain "Vincristine" as an active ingredient.
FDA Label Search

PubMed references

The following resource link will perform a PubMed query for the terms "Vincristine" and "liver toxicity".
Vincristine Search


  1. Feldmann, G., 2006. Liver apoptosis. Gastroenterol. Clin. Biol. 30, 533–545.
  2. Gomez-Lechon, M.J., O’Connor, E., Castell, J.V., Jover, R., 2002. Sensitive markers used to identify compounds that trigger apoptosis in cultured hepatocytes. Toxicol. Sci. 65, 299–308.
  3. Gomez-Lechon, M.J., O’Connor, J.E., Lahoz, A., Castell, J.V., Donato, M.T., 2008. Identification of apoptotic drugs: multiparametric evaluation in cultured hepatocytes. Curr. Med. Chem. 15, 2071–2085.
  4. Gomez-Lechon, M.J., Ponsoda, X., O’Connor, E., Donato, T., Jover, R., Castell, J.V., 2003. Diclofenac induces apoptosis in hepatocytes. Toxicol. in Vitro 17, 675– 680.
  5. Kass, G.E., Macanas-Pirard, P., Lee, P.C., Hinton, R.H., 2003. The role of apoptosis in acetaminophen-induced injury. Ann. NY Acad. Sci. 1010, 557–559.

Calculated/Predicted Properties

Water Solubility Results
pH Sol,mg/ml Flags  % Graph
2 54.05 B 100 Vincristine solubility.png
5.5 1.72 B 100
6.5 9.91E-2 BN 96/4
7.4 1.51E-2 BN 72/28
10 4.63E-3 AN 6/93
Summary Solubility Data
Intrinsic Solubility,mg/ml 4.3026E-3
Intrinsic Solubility,log(S,mol/l) -5.2827
Solubility in Pure Water at pH = 8.26,mg/ml 5.7934E-3
Calculations performed using ACD/PhysChem v 9.14
Single-valued Properties
Property Value Units Error
Molar Refractivity 221.09 cm3 0.4
Molar Volume 586.86 cm3 5
Parachor 1721.57 cm3 6
Index of Refraction 1.68 3.33E-2
Surface Tension 74.06 dyne/cm 5
Density 1.41 g/cm3 0.1
Polarizability 87.65 10E-24 cm3 0.5
Calculations performed using ACD/PhysChem v 9.14
Property Name Value Units Source
pKa - SPARC v4.5
Estimated VP 4.78E-29 mm Hg EPI Suite v4.10
Estimated VP 6.37E-27 Pa EPI Suite v4.10
Estimated Water Solubility 0.1152 mg/L EPI Suite v4.10
WATERNT Frag Water Solubility Estimate 0.4825 mg/L EPI Suite v4.10
pKa Results
Acidic/Basic Acidic/Basic Aparrent pKa Value Error
40 A 16.7 0.6
59 A 14.61 0.4
18 MA 11.1 0.6
53 MB 7.9 0.6
7 B 5.54 0.7
40 B -2.95 0.6
9 B -4.58 0.7
A = Acidic
B = Basic
MA = Most Acidic
MB = Most Basic
Calculations performed using ACD/PhysChem v 9.14

Authors of this ToxBank wiki page

David Bower, Egon Willighagen, Matthew Clark
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