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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyVadimezan
Identification
- Name
- Vadimezan
- Accession Number
- DB06235 (DB13081)
- Type
- Small Molecule
- Groups
- Investigational
- Description
- Not Available
- Structure
Structure for DB06235 (Vadimezan)
- Synonyms
- AS1404
- DMXAA
- External IDs
- AS-1404 / ASA-404 / ASA404 / NSC-640488
- Product Ingredients
Ingredient UNII CAS InChI Key Vadimezan Sodium C35T92HIZM 129095-08-5 CUHSZPRXKQDLCJ-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.
- 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
Drug Interaction Drug group Abiraterone The serum concentration of Vadimezan can be increased when it is combined with Abiraterone. Approved Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Vadimezan. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Vadimezan. Experimental Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Vadimezan. Approved, Investigational, Withdrawn Azithromycin The metabolism of Vadimezan can be decreased when combined with Azithromycin. Approved Bevacizumab Bevacizumab may increase the cardiotoxic activities of Vadimezan. Approved, Investigational Bortezomib The metabolism of Vadimezan can be decreased when combined with Bortezomib. Approved, Investigational Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Vadimezan. Approved Caffeine The metabolism of Vadimezan can be decreased when combined with Caffeine. Approved Citalopram The metabolism of Vadimezan can be decreased when combined with Citalopram. Approved Clotrimazole The metabolism of Vadimezan can be decreased when combined with Clotrimazole. Approved, Vet Approved Curcumin The metabolism of Vadimezan can be decreased when combined with Curcumin. Approved, Investigational Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Vadimezan. Approved, Investigational Cymarin Cymarin may decrease the cardiotoxic activities of Vadimezan. Experimental Cyproterone acetate The serum concentration of Vadimezan can be decreased when it is combined with Cyproterone acetate. Approved, Investigational Deferasirox The serum concentration of Vadimezan can be increased when it is combined with Deferasirox. Approved, Investigational Deslanoside Deslanoside may decrease the cardiotoxic activities of Vadimezan. Approved Digitoxin Digitoxin may decrease the cardiotoxic activities of Vadimezan. Approved, Investigational Digoxin Digoxin may decrease the cardiotoxic activities of Vadimezan. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Vadimezan. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Vadimezan. Approved, Investigational Dosulepin The metabolism of Vadimezan can be decreased when combined with Dosulepin. Approved Fluvoxamine The metabolism of Vadimezan can be decreased when combined with Fluvoxamine. Approved, Investigational Gitoformate Gitoformate may decrease the cardiotoxic activities of Vadimezan. Experimental Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Vadimezan. Experimental Lidocaine The metabolism of Vadimezan can be decreased when combined with Lidocaine. Approved, Vet Approved Lobeglitazone The metabolism of Vadimezan can be decreased when combined with Lobeglitazone. Approved, Investigational Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Vadimezan. Experimental Mexiletine The metabolism of Vadimezan can be decreased when combined with Mexiletine. Approved, Investigational Midostaurin The metabolism of Vadimezan can be decreased when combined with Midostaurin. Approved, Investigational Nevirapine The metabolism of Vadimezan can be decreased when combined with Nevirapine. Approved Oleandrin Oleandrin may decrease the cardiotoxic activities of Vadimezan. Experimental, Investigational Osimertinib The serum concentration of Vadimezan can be decreased when it is combined with Osimertinib. Approved Ouabain Ouabain may decrease the cardiotoxic activities of Vadimezan. Approved Paclitaxel The risk or severity of adverse effects can be increased when Paclitaxel is combined with Vadimezan. Approved, Vet Approved Peginterferon alfa-2b The serum concentration of Vadimezan can be increased when it is combined with Peginterferon alfa-2b. Approved Peruvoside Peruvoside may decrease the cardiotoxic activities of Vadimezan. Experimental Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Vadimezan. Experimental Ropinirole The metabolism of Vadimezan can be decreased when combined with Ropinirole. Approved, Investigational Rucaparib The metabolism of Vadimezan can be decreased when combined with Rucaparib. Approved, Investigational Simeprevir The metabolism of Vadimezan can be decreased when combined with Simeprevir. Approved Tenofovir disoproxil The metabolism of Vadimezan can be decreased when combined with Tenofovir disoproxil. Approved, Investigational Teriflunomide The serum concentration of Vadimezan can be decreased when it is combined with Teriflunomide. Approved Theophylline The metabolism of Vadimezan can be decreased when combined with Theophylline. Approved Ticlopidine The metabolism of Vadimezan can be decreased when combined with Ticlopidine. Approved Trastuzumab Trastuzumab may increase the cardiotoxic activities of Vadimezan. Approved, Investigational Vemurafenib The serum concentration of Vadimezan can be increased when it is combined with Vemurafenib. Approved Zucapsaicin The metabolism of Vadimezan can be decreased when combined with Zucapsaicin. Approved, Investigational - Food Interactions
- Not Available
References
- General References
- 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]
- 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]
- Link [Link]
- External Links
- PDB Entries
- 4lol / 4qxo / 4qxp / 4qxq / 4qxr
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Advanced or Recurrent Solid Tumors 1 1 Completed Treatment Lung Cancer Non-Small Cell Cancer (NSCLC) 1 1 Completed Treatment Refractory Tumors 1 1 Completed Treatment Tumors, Solid 1 1 Completed Treatment Unspecified Adult Solid Tumor, Protocol Specific 1 1 Terminated Treatment Advanced Solid Tumors 1 1 Terminated Treatment Histologically-proven and Radiologically-confirmed Solid Tumors 1 1 Terminated Treatment Metastatic Cancer With Impaired Renal Function / Metastatic Cancer With Normal Renal Function 1 1 Terminated Treatment Solid Tumor Malignancies 1 1 Terminated Treatment Tumors, Solid 1 1 Withdrawn Treatment Tumors 1 2 Completed Treatment Lung Cancers 1 2 Completed Treatment Prostate Cancer 1 2 Withdrawn Treatment Transitional Cell Carcinoma 1 3 Terminated Treatment Lung 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
Property Value Source Water Solubility 0.0225 mg/mL ALOGPS logP 3.06 ALOGPS logP 3.62 ChemAxon logS -4.1 ALOGPS pKa (Strongest Acidic) 3.6 ChemAxon pKa (Strongest Basic) -7.7 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 63.6 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 78.21 m3·mol-1 ChemAxon Polarizability 29.37 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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 July 02, 2018 20:53