Camptothecin

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Camptothecin
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Camptothecin
Camptothecin.png
Identifiers
Leadscope Id LS-1706
CAS 7689-03-4
ChemSpider 22775
Pathway DBs
Assay DBs
PubChem CID 2538
ChEMBL 65
Omics DBs
Properties
ToxCast Accepted no
Toxic Effect Apoptosis
ToxBank Accepted no
Target DNA topoisomerase I


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 CCC1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)O
InChI

InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1

InChI-Key

VSJKWCGYPAHWDS-FQEVSTJZSA-N

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] [6] [7] [8]

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
1.
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.
2.
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.
3.
Literature data for at least one, but not necessarily all, of the ‘omics datasets is desired. This requirement can be waived in special cases.
4.
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.
5.
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.
6.
Sparing soluble compounds may be assayed for solubility in serum and the percent serum used specified here.
7.
This property will be measured when a sample of compound becomes available.

Proprietary Toxicity Literature Report

Currently Unavailable

PubMed references

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

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Feldmann, G., 2006. Liver apoptosis. Gastroenterol. Clin. Biol. 30, 533–545.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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
2 559.29 B 100 Camptothecin solubility.png
5.5 3.34 BN 14/86
6.5 2.94 N 98
7.4 2.9 N 100
10 3.09 AN 6/94
Summary Solubility Data
Intrinsic Solubility,mg/ml 2.8914
Intrinsic Solubility,log(S,mol/l) -2.0809
Solubility in Pure Water at pH = 7.9,mg/ml 2.8947
Calculations performed using ACD/PhysChem v 9.14
Single-valued Properties
Property Value Units Error
Molar Refractivity 93.45 cm3 0.4
Molar Volume 230.22 cm3 5
Parachor 688.9 cm3 6
Index of Refraction 1.75 3.33E-2
Surface Tension 80.18 dyne/cm 5
Density 1.51 g/cm3 0.1
Polarizability 37.04 10E-24 cm3 0.5
Calculations performed using ACD/PhysChem v 9.14
Property Name Value Units Source
pKa - SPARC v4.5
Estimated VP 3.76E-15 mm Hg EPI Suite v4.10
Estimated VP 5.01E-13 Pa EPI Suite v4.10
Estimated Water Solubility 207 mg/L EPI Suite v4.10
WATERNT Frag Water Solubility Estimate 39991 mg/L EPI Suite v4.10
pKa Results
Acidic/Basic Acidic/Basic Aparrent pKa Value Error
26 MA 11.24 0.2
22 MB 4.76 0.4
12 B -2.84 0.4
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
Retrieved from "http://wiki.toxbank.net/wiki/Camptothecin"
Facts about CamptothecinRDF feed
Accepted by ToxBankno  +
Accepted by ToxCastno  +
Equivalent URIThis property is a special property in this wiki.http://bio2rdf.org/cas:7689-03-4  +, http://www.chemspider.com/Chemical-Structure.22775.rdf  +, http://bio2rdf.org/pubchem:2538  +, and http://rdf.openmolecules.net/?InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1  +
Has CAS7689-03-4  +
Has ChEMBL Id65  +
Has ChemSpider Id22775  +
Has InChIInChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1  +
Has InChIKeyVSJKWCGYPAHWDS-FQEVSTJZSA-N  +
Has Leadscope IdLS-1706  +
Has PubChem CID2538  +
Has Smilesc12c(c(n3Cc4c(c3c2)nc2ccccc2c4)=O)COC([C@@]1(CC)O)=O  +
Has categoryHepatotoxic  +
Has imageCamptothecin.png  +
Has targetDNA topoisomerase I  +
Has toxic effectApoptosis  +
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