combretastatin A4   Click here for help

GtoPdb Ligand ID: 8854

Synonyms: CA-4 | combretastatin A-4 | NSC-613729
PDB Ligand
Compound class: Synthetic organic
Comment: Combretastatin A4 is the active metabolite of 8857. Combretastatin A4 interacts with the colchicine binding site of tubulin, which primarily resides within the β-tubulin subunit, at its interface with the α-subunit [3]. The compound has antineoplastic activity, inhibiting microtubule polymerization, and causing mitotic arrest and apoptosis, particularly targeting the tumour vasculature [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 0
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 57.15
Molecular weight 316.13
XLogP 3.64
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc(C=Cc2ccc(c(c2)O)OC)cc(c1OC)OC
Isomeric SMILES COc1cc(/C=C\c2ccc(c(c2)O)OC)cc(c1OC)OC
InChI InChI=1S/C18H20O5/c1-20-15-8-7-12(9-14(15)19)5-6-13-10-16(21-2)18(23-4)17(11-13)22-3/h5-11,19H,1-4H3/b6-5-
1. Gangjee A, Zhao Y, Raghavan S, Rohena CC, Mooberry SL, Hamel E. (2013)
Structure-activity relationship and in vitro and in vivo evaluation of the potent cytotoxic anti-microtubule agent N-(4-methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium chloride and its analogues as antitumor agents.
J Med Chem, 56 (17): 6829-44. [PMID:23895532]
2. Griggs J, Metcalfe JC, Hesketh R. (2001)
Targeting tumour vasculature: the development of combretastatin A4.
Lancet Oncol, 2 (2): 82-7. [PMID:11905799]
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]