Vadimezan - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Spectra Taxonomy

Enzymes (3)

Enzymes (3)Biointeractions (2)

Identification

Name

Vadimezan

Accession Number

DB06235 (DB13081)

Type

Small Molecule

Groups

Investigational

Description

Not Available

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

AS1404

DMXAA

External IDs

AS-1404 / ASA-404 / ASA404 / NSC-640488

Product Ingredients

Ingredient	UNII	CAS	InChI Key	Details
Vadimezan Sodium	C35T92HIZM	129095-08-5	CUHSZPRXKQDLCJ-UHFFFAOYSA-M	Details

Approved Prescription Products

Not Available

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Not Available

Brand mixtures

Not Available

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

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

Drug	Interaction	Drug group
Abiraterone	The serum concentration of ASA404 can be increased when it is combined with Abiraterone.	Approved
Acetyldigitoxin	Acetyldigitoxin may decrease the cardiotoxic activities of ASA404.	Approved
Azithromycin	The metabolism of ASA404 can be decreased when combined with Azithromycin.	Approved
Bevacizumab	Bevacizumab may increase the cardiotoxic activities of ASA404.	Approved, Investigational
Bortezomib	The metabolism of ASA404 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 ASA404.	Approved
Caffeine	The metabolism of ASA404 can be decreased when combined with Caffeine.	Approved
Carbamazepine	The metabolism of ASA404 can be increased when combined with Carbamazepine.	Approved, Investigational
Citalopram	The metabolism of ASA404 can be decreased when combined with Citalopram.	Approved
Clotrimazole	The metabolism of ASA404 can be decreased when combined with Clotrimazole.	Approved, Vet Approved
Cyclophosphamide	Cyclophosphamide may increase the cardiotoxic activities of ASA404.	Approved, Investigational
Cyproterone acetate	The serum concentration of ASA404 can be decreased when it is combined with Cyproterone acetate.	Approved, Investigational
Deferasirox	The serum concentration of ASA404 can be increased when it is combined with Deferasirox.	Approved, Investigational
Deslanoside	Deslanoside may decrease the cardiotoxic activities of ASA404.	Approved
Digitoxin	Digitoxin may decrease the cardiotoxic activities of ASA404.	Approved
Digoxin	Digoxin may decrease the cardiotoxic activities of ASA404.	Approved
Docetaxel	The risk or severity of adverse effects can be increased when Docetaxel is combined with ASA404.	Approved, Investigational
Fluvoxamine	The metabolism of ASA404 can be decreased when combined with Fluvoxamine.	Approved, Investigational
Lidocaine	The metabolism of ASA404 can be decreased when combined with Lidocaine.	Approved, Vet Approved
Mexiletine	The metabolism of ASA404 can be decreased when combined with Mexiletine.	Approved
Nevirapine	The metabolism of ASA404 can be decreased when combined with Nevirapine.	Approved
Oleandrin	Anvirzel may decrease the cardiotoxic activities of ASA404.	Experimental
Osimertinib	The serum concentration of ASA404 can be decreased when it is combined with Osimertinib.	Approved
Ouabain	Ouabain may decrease the cardiotoxic activities of ASA404.	Approved
Paclitaxel	The risk or severity of adverse effects can be increased when Paclitaxel is combined with ASA404.	Approved, Vet Approved
Peginterferon alfa-2b	The serum concentration of ASA404 can be increased when it is combined with Peginterferon alfa-2b.	Approved
Phenobarbital	The metabolism of ASA404 can be increased when combined with Phenobarbital.	Approved
Primidone	The metabolism of ASA404 can be increased when combined with Primidone.	Approved, Vet Approved
Rifampicin	The metabolism of ASA404 can be increased when combined with Rifampicin.	Approved
Ropinirole	The metabolism of ASA404 can be decreased when combined with Ropinirole.	Approved, Investigational
Simeprevir	The metabolism of ASA404 can be decreased when combined with Simeprevir.	Approved
Tenofovir disoproxil	The metabolism of ASA404 can be decreased when combined with Tenofovir.	Approved, Investigational
Teriflunomide	The serum concentration of ASA404 can be decreased when it is combined with Teriflunomide.	Approved
Theophylline	The metabolism of ASA404 can be decreased when combined with Theophylline.	Approved
Ticlopidine	The metabolism of ASA404 can be decreased when combined with Ticlopidine.	Approved
Trastuzumab	Trastuzumab may increase the cardiotoxic activities of ASA404.	Approved, Investigational
Vemurafenib	The serum concentration of ASA404 can be increased when it is combined with Vemurafenib.	Approved

Food Interactions

Not Available

References

Synthesis Reference

Not Available

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

Resource	Link
ChemSpider	110486
ChEBI	75934
ChEMBL	CHEMBL71263
HET	1YE

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Treatment	Advanced or Recurrent Solid Tumors	1
1	Completed	Treatment	Non-Small-Cell Lung Carcinoma (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	Non-Small-Cell Lung Carcinoma (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 Type	Description	Splash Key
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	Not Available
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	Not Available

Taxonomy

Description

This 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.

Kingdom

Chemical entities

Super Class

Organic compounds

Class

Organoheterocyclic compounds

Sub Class

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

Details

1. UDP-glucuronosyltransferase 1-9

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

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 ]

Details

2. UDP-glucuronosyltransferase 2B7

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

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 ]

Details

3. Cytochrome P450 1A2

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

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 September 01, 2017 11:27

Structure for DB06235 (Vadimezan)

Enzymes

References

References

References