Identification

Name
Vadimezan
Accession Number
DB06235  (DB13081)
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • AS1404
  • DMXAA
External IDs
AS-1404 / ASA-404 / ASA404 / NSC-640488
Product Ingredients
IngredientUNIICASInChI Key
Vadimezan SodiumC35T92HIZM129095-08-5CUHSZPRXKQDLCJ-UHFFFAOYSA-M
Categories
UNII
0829J8133H
CAS number
Not Available
Weight
Average: 282.2907
Monoisotopic: 282.089208936
Chemical Formula
C17H14O4
InChI Key
XGOYIMQSIKSOBS-UHFFFAOYSA-N
InChI
InChI=1S/C17H14O4/c1-9-6-7-13-15(20)12-5-3-4-11(8-14(18)19)17(12)21-16(13)10(9)2/h3-7H,8H2,1-2H3,(H,18,19)
IUPAC Name
2-(5,6-dimethyl-9-oxo-9H-xanthen-4-yl)acetic acid
SMILES
CC1=C(C)C2=C(C=C1)C(=O)C1=CC=CC(CC(O)=O)=C1O2

Pharmacology

Indication

Investigated for use/treatment in solid tumors, lung cancer, ovarian cancer, and prostate cancer.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

ASA404 (DMXAA) is a small-molecule vascular disrupting agent which targets the blood vessels that nourish tumours. The proposed mechanism of action for ASA404 is directly increasing permeability of the tumor's endothelial cells. Vasoactive mediators such as tumor necrosis factor (TNF) may also be implicated. Increased permeability of tumor cell vasculature may allow increased permeation of anticancer treatments such as cytotoxic drugs, antibodies, drug conjugates and gene therapy.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
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
DrugInteractionDrug group
AbirateroneThe serum concentration of Vadimezan can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Vadimezan.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Vadimezan.Experimental
AzithromycinThe metabolism of Vadimezan can be decreased when combined with Azithromycin.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Vadimezan.Approved, Investigational
BortezomibThe metabolism of Vadimezan can be decreased when combined with Bortezomib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vadimezan.Approved
CaffeineThe metabolism of Vadimezan can be decreased when combined with Caffeine.Approved
CitalopramThe metabolism of Vadimezan can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of Vadimezan can be decreased when combined with Clotrimazole.Approved, Vet Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Vadimezan.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Vadimezan.Experimental
Cyproterone acetateThe serum concentration of Vadimezan can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of Vadimezan can be increased when it is combined with Deferasirox.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Vadimezan.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Vadimezan.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Vadimezan.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Vadimezan.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Vadimezan.Approved, Investigational
DosulepinThe metabolism of Vadimezan can be decreased when combined with Dosulepin.Approved
FluvoxamineThe metabolism of Vadimezan can be decreased when combined with Fluvoxamine.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Vadimezan.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Vadimezan.Experimental
LidocaineThe metabolism of Vadimezan can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Vadimezan can be decreased when combined with Lobeglitazone.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Vadimezan.Experimental
MexiletineThe metabolism of Vadimezan can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Vadimezan can be decreased when combined with Midostaurin.Approved
NevirapineThe metabolism of Vadimezan can be decreased when combined with Nevirapine.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Vadimezan.Experimental, Investigational
OsimertinibThe serum concentration of Vadimezan can be decreased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Vadimezan.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Vadimezan.Approved, Vet Approved
Peginterferon alfa-2bThe serum concentration of Vadimezan can be increased when it is combined with Peginterferon alfa-2b.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Vadimezan.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Vadimezan.Experimental
RopiniroleThe metabolism of Vadimezan can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of Vadimezan can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of Vadimezan can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Vadimezan can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Vadimezan can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Vadimezan can be decreased when combined with Ticlopidine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Vadimezan.Approved, Investigational
VemurafenibThe serum concentration of Vadimezan can be increased when it is combined with Vemurafenib.Approved
ZucapsaicinThe metabolism of Vadimezan can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

General References
  1. Zhao L, Ching LM, Kestell P, Kelland LR, Baguley BC: Mechanisms of tumor vascular shutdown induced by 5,6-dimethylxanthenone-4-acetic acid (DMXAA): Increased tumor vascular permeability. Int J Cancer. 2005 Aug 20;116(2):322-6. [PubMed:15800918]
  2. McKeage MJ: The potential of DMXAA (ASA404) in combination with docetaxel in advanced prostate cancer. Expert Opin Investig Drugs. 2008 Jan;17(1):23-9. [PubMed:18095916]
  3. Link [Link]
External Links
PubChem Compound
123964
PubChem Substance
347827766
ChemSpider
110486
ChEBI
75934
ChEMBL
CHEMBL71263
HET
1YE
PDB Entries
4lol / 4qxo / 4qxp / 4qxq / 4qxr

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced or Recurrent Solid Tumors1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentRefractory Tumors1
1CompletedTreatmentTumors, Solid1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
1TerminatedTreatmentAdvanced Solid Tumors1
1TerminatedTreatmentHistologically-proven and Radiologically-confirmed Solid Tumors1
1TerminatedTreatmentMetastatic Cancer With Impaired Renal Function / Metastatic Cancer With Normal Renal Function1
1TerminatedTreatmentSolid Tumor Malignancies1
1TerminatedTreatmentTumors, Solid1
1WithdrawnTreatmentTumors1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentProstate Cancer1
2WithdrawnTreatmentTransitional Cell Carcinoma1
3TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)2

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 Solubility0.0225 mg/mLALOGPS
logP3.06ALOGPS
logP3.62ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)3.6ChemAxon
pKa (Strongest Basic)-7.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity78.21 m3·mol-1ChemAxon
Polarizability29.37 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 xanthones. These are polycyclic aromatic compounds containing a xanthene moiety conjugated to a ketone group at carbon 9. Xanthene is a tricyclic compound made up of two benzene rings linearly fused to each other through a pyran ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
Xanthones
Alternative Parents
Chromones / Pyranones and derivatives / Benzenoids / Heteroaromatic compounds / Oxacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Xanthone / Chromone / Pyranone / Pyran / Benzenoid / Heteroaromatic compound / Monocarboxylic acid or derivatives / Carboxylic acid / Carboxylic acid derivative / Oxacycle
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid, xanthones (CHEBI:75934)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Zhou S, Kestell P, Baguley BC, Paxton JW: 5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy. Invest New Drugs. 2002 Aug;20(3):281-95. [PubMed:12201491]
  2. Zhou S, Kestell P, Paxton JW: Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation. Drug Metab Rev. 2002 Nov;34(4):751-90. [PubMed:12487149]
  3. Miners JO, Valente L, Lillywhite KJ, Mackenzie PI, Burchell B, Baguley BC, Kestell P: Preclinical prediction of factors influencing the elimination of 5,6-dimethylxanthenone-4-acetic acid, a new anticancer drug. Cancer Res. 1997 Jan 15;57(2):284-9. [PubMed:9000569]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Zhou S, Paxton JW, Tingle MD, Kestell P: Identification of the human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5,6-dimethylxanthenone-4-acetic acid. Drug Metab Dispos. 2000 Dec;28(12):1449-56. [PubMed:11095582]
  2. Zhou S, Kestell P, Baguley BC, Paxton JW: Preclinical factors affecting the interindividual variability in the clearance of the investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid. Biochem Pharmacol. 2003 Jun 1;65(11):1853-65. [PubMed:12781337]
  3. Zhou S, Kestell P, Baguley BC, Paxton JW: 5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy. Invest New Drugs. 2002 Aug;20(3):281-95. [PubMed:12201491]
  4. Zhou S, Kestell P, Paxton JW: Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation. Drug Metab Rev. 2002 Nov;34(4):751-90. [PubMed:12487149]
  5. Miners JO, Valente L, Lillywhite KJ, Mackenzie PI, Burchell B, Baguley BC, Kestell P: Preclinical prediction of factors influencing the elimination of 5,6-dimethylxanthenone-4-acetic acid, a new anticancer drug. Cancer Res. 1997 Jan 15;57(2):284-9. [PubMed:9000569]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zhou S, Paxton JW, Tingle MD, Kestell P: Identification of the human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5,6-dimethylxanthenone-4-acetic acid. Drug Metab Dispos. 2000 Dec;28(12):1449-56. [PubMed:11095582]
  2. Zhou S, Kestell P, Baguley BC, Paxton JW: Preclinical factors affecting the interindividual variability in the clearance of the investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid. Biochem Pharmacol. 2003 Jun 1;65(11):1853-65. [PubMed:12781337]
  3. Zhou S, Kestell P, Baguley BC, Paxton JW: 5,6-dimethylxanthenone-4-acetic acid (DMXAA): a new biological response modifier for cancer therapy. Invest New Drugs. 2002 Aug;20(3):281-95. [PubMed:12201491]
  4. Zhou S, Kestell P, Paxton JW: Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation. Drug Metab Rev. 2002 Nov;34(4):751-90. [PubMed:12487149]

Drug created on March 19, 2008 10:18 / Updated on November 09, 2017 03:53