Identification
NameVadimezan
Accession NumberDB06235  (DB13081)
TypeSmall Molecule
GroupsInvestigational
DescriptionNot Available
Structure
Thumb
Synonyms
AS1404
DMXAA
External IDs AS-1404 / ASA-404 / ASA404 / NSC-640488
Product Ingredients
IngredientUNIICASInChI KeyDetails
Vadimezan SodiumC35T92HIZM 129095-08-5CUHSZPRXKQDLCJ-UHFFFAOYSA-MDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII0829J8133H
CAS numberNot Available
WeightAverage: 282.2907
Monoisotopic: 282.089208936
Chemical FormulaC17H14O4
InChI KeyXGOYIMQSIKSOBS-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
PharmacodynamicsNot 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.

Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of ASA404 can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of ASA404.Approved
AzithromycinThe metabolism of ASA404 can be decreased when combined with Azithromycin.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of ASA404.Approved, Investigational
BortezomibThe metabolism of ASA404 can be decreased when combined with Bortezomib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with ASA404.Approved
CaffeineThe metabolism of ASA404 can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of ASA404 can be increased when combined with Carbamazepine.Approved, Investigational
CitalopramThe metabolism of ASA404 can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of ASA404 can be decreased when combined with Clotrimazole.Approved, Vet Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of ASA404.Approved, Investigational
Cyproterone acetateThe serum concentration of ASA404 can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of ASA404 can be increased when it is combined with Deferasirox.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of ASA404.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of ASA404.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of ASA404.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with ASA404.Approved, Investigational
FluvoxamineThe metabolism of ASA404 can be decreased when combined with Fluvoxamine.Approved, Investigational
LidocaineThe metabolism of ASA404 can be decreased when combined with Lidocaine.Approved, Vet Approved
MexiletineThe metabolism of ASA404 can be decreased when combined with Mexiletine.Approved
NevirapineThe metabolism of ASA404 can be decreased when combined with Nevirapine.Approved
OleandrinAnvirzel may decrease the cardiotoxic activities of ASA404.Experimental
OsimertinibThe serum concentration of ASA404 can be decreased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of ASA404.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with ASA404.Approved, Vet Approved
Peginterferon alfa-2bThe serum concentration of ASA404 can be increased when it is combined with Peginterferon alfa-2b.Approved
PhenobarbitalThe metabolism of ASA404 can be increased when combined with Phenobarbital.Approved
PrimidoneThe metabolism of ASA404 can be increased when combined with Primidone.Approved, Vet Approved
RifampicinThe metabolism of ASA404 can be increased when combined with Rifampicin.Approved
RopiniroleThe metabolism of ASA404 can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of ASA404 can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of ASA404 can be decreased when combined with Tenofovir.Approved, Investigational
TeriflunomideThe serum concentration of ASA404 can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of ASA404 can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of ASA404 can be decreased when combined with Ticlopidine.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of ASA404.Approved, Investigational
VemurafenibThe serum concentration of ASA404 can be increased when it is combined with Vemurafenib.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAdvanced or Recurrent Solid Tumors1
1CompletedTreatmentNon-Small-Cell Lung Carcinoma (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
3TerminatedTreatmentNon-Small-Cell Lung Carcinoma (NSCLC)2
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassBenzopyrans
Direct ParentXanthones
Alternative ParentsChromones / Pyranones and derivatives / Benzenoids / Heteroaromatic compounds / Oxacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
SubstituentsXanthone / Chromone / Pyranone / Pyran / Benzenoid / Heteroaromatic compound / Monocarboxylic acid or derivatives / Carboxylic acid / Carboxylic acid derivative / Oxacycle
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsmonocarboxylic 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 transferase activity but acts as a negative regulator of isoform 1.
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 suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol...
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
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 September 01, 2017 11:27