fosbretabulin   Click here for help

GtoPdb Ligand ID: 8857

Synonyms: CA4DP | combretastatin A4 phosphate | fosbretabulin disodium | fosbretabulin tromethamine | Zybrestat (fosbretabulin disodium)
Compound class: Synthetic organic
Comment: Fosbretabulin is being investigated for anti-tumour potential. It interferes with vascularisation by preventing tubulin-polymerisation and disrupting cell junctions [2]. This action destroys tumour vasculature and leads to cancer cell death and necrosis. Mechanistically, fosbretabulin is dephosphorylated to the active tubulin polymerisation inhibitor combretastatin A4 [3]. The compound was originally isolated from the African bush willow (Combretum caffrum) [1,5].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 113.49
Molecular weight 396.1
XLogP 2.21
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1cc(C=Cc2ccc(c(c2)OP(=O)(O)O)OC)cc(c1OC)OC
Isomeric SMILES COc1cc(/C=C\c2ccc(c(c2)OP(=O)(O)O)OC)cc(c1OC)OC
InChI InChI=1S/C18H21O8P/c1-22-14-8-7-12(9-15(14)26-27(19,20)21)5-6-13-10-16(23-2)18(25-4)17(11-13)24-3/h5-11H,1-4H3,(H2,19,20,21)/b6-5-
InChI Key WDOGQTQEKVLZIJ-WAYWQWQTSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Various formulations of fosbretabulin have been advanced to clinical evaluations to determine safety and efficacy against solid tumours.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01305213 Bevacizumab With or Without Fosbretabulin Tromethamine in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer Phase 2 Interventional National Cancer Institute (NCI) In this study fosbretabulin was investigated for anti-tumour efficacy in combination with the anti-VEGFA agent ; fosbretabulin to damage existing tumour vasculature and bevacizumab to disrupt revascularisation. 4
NCT00653939 A Safety and Efficacy Study of Carboplatin, Paclitaxel, Bevacizumab and CA4P in Non-Small Cell Lung Cancer Phase 2 Interventional Mateon Therapeutics