Identification

Name
CA4P
Accession Number
DB05284
Type
Small Molecule
Groups
Investigational
Description

CA4P (Combretastatin)has been shown in the laboratory to shut down the blood supply to tumours. It is one of the first vascular targeting drugs to be tested in patients. This drug was originally isolated from the African Bush Willow. The first studies in patients with this drug were aimed at finding out whether it can be safely given to patients, what side effects it produces and whether it can actually shut down the blood supply to human tumours.

Structure
Thumb
Synonyms
Not Available
Categories
Not Available
UNII
Not Available
CAS number
Not Available
Weight
Average: 334.3637
Monoisotopic: 334.141638436
Chemical Formula
C18H22O6
InChI Key
LGZKGOGODCLQHG-ZDUSSCGKSA-N
InChI
InChI=1S/C18H22O6/c1-21-15-6-5-11(8-14(15)20)7-13(19)12-9-16(22-2)18(24-4)17(10-12)23-3/h5-6,8-10,13,19-20H,7H2,1-4H3/t13-/m0/s1
IUPAC Name
5-[(2S)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol
SMILES
COC1=CC(=CC(OC)=C1OC)[C@@H](O)CC1=CC(O)=C(OC)C=C1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action

CA4P binds tubulin with a higher efficacy than colchicines, and was therefore initially investigated as an anti-mitotic agent. However, it was later observed to also induce vascular shutdown and necrosis in tumours. Clinical trials have revealed its positive effects, either as a single agent or in combination with chemotherapy, in patients with ovarian, lung or anaplastic thyroid cancer. Biochemical analyses revealed that CA4P rapidly diminished the tyrosine phosphorylation of VE-cadherin and beta-catenin, thereby blocking the endothelial signalling pathway that is necessary for maintaining a functional endothelial cell structure and survival.

TargetActionsOrganism
UTubulin beta chainNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

References

General References
  1. Petit I, Karajannis MA, Vincent L, Young L, Butler J, Hooper AT, Shido K, Steller H, Chaplin DJ, Feldman E, Rafii S: The microtubule-targeting agent CA4P regresses leukemic xenografts by disrupting interaction with vascular cells and mitochondrial-dependent cell death. Blood. 2008 Feb 15;111(4):1951-61. Epub 2007 Nov 16. [PubMed:18024794]
External Links
PubChem Compound
100154
PubChem Substance
175426964
ChemSpider
90508
Wikipedia
Combretastatin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0545 mg/mLALOGPS
logP2.23ALOGPS
logP2.34ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)9.99ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area77.38 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity89.75 m3·mol-1ChemAxon
Polarizability34.48 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8812
Blood Brain Barrier+0.623
Caco-2 permeable+0.6844
P-glycoprotein substrateSubstrate0.5603
P-glycoprotein inhibitor INon-inhibitor0.6316
P-glycoprotein inhibitor IIInhibitor0.5186
Renal organic cation transporterNon-inhibitor0.8798
CYP450 2C9 substrateNon-substrate0.7495
CYP450 2D6 substrateNon-substrate0.7875
CYP450 3A4 substrateSubstrate0.5304
CYP450 1A2 substrateInhibitor0.645
CYP450 2C9 inhibitorNon-inhibitor0.8555
CYP450 2D6 inhibitorNon-inhibitor0.5144
CYP450 2C19 inhibitorInhibitor0.7786
CYP450 3A4 inhibitorNon-inhibitor0.7694
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5604
Ames testNon AMES toxic0.8759
CarcinogenicityNon-carcinogens0.8488
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity2.5923 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9438
hERG inhibition (predictor II)Non-inhibitor0.8336
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Methoxyphenols / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Secondary alcohols / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Stilbene / Methoxyphenol / Phenoxy compound / Anisole / Methoxybenzene / Phenol ether / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Alkyl aryl ether / Phenol
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ubiquitin protein ligase binding
Specific Function
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name
TUBB
Uniprot ID
P07437
Uniprot Name
Tubulin beta chain
Molecular Weight
49670.515 Da

Drug created on November 18, 2007 11:23 / Updated on March 01, 2020 19:31

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