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 CDK toolkit. 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
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.

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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
References
1. Cirla A, Mann J. (2003)
Combretastatins: from natural products to drug discovery.
Nat Prod Rep, 20 (6): 558-64. [PMID:14700199]
2. Kanthou C, Tozer GM. (2009)
Microtubule depolymerizing vascular disrupting agents: novel therapeutic agents for oncology and other pathologies.
Int J Exp Pathol, 90 (3): 284-94. [PMID:19563611]
3. Lin CM, Singh SB, Chu PS, Dempcy RO, Schmidt JM, Pettit GR, Hamel E. (1988)
Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study.
Mol Pharmacol, 34 (2): 200-8. [PMID:3412321]
4. Monk BJ, Sill MW, Walker JL, Darus CJ, Sutton G, Tewari KS, Martin LP, Schilder JM, Coleman RL, Balkissoon J et al.. (2016)
Randomized Phase II Evaluation of Bevacizumab Versus Bevacizumab Plus Fosbretabulin in Recurrent Ovarian, Tubal, or Peritoneal Carcinoma: An NRG Oncology/Gynecologic Oncology Group Study.
J Clin Oncol, 34 (19): 2279-86. [PMID:27217446]
5. Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D. (1989)
Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4.
Experientia, 45 (2): 209-11. [PMID:2920809]