DMXAA (Vadimezan)

Modify Date: 2024-01-02 23:02:32

DMXAA (Vadimezan) structure	Common Name	DMXAA (Vadimezan)
	CAS Number	117570-53-3	Molecular Weight	282.291
	Density	1.3±0.1 g/cm3	Boiling Point	520.9±50.0 °C at 760 mmHg
	Molecular Formula	C₁₇H₁₄O₄	Melting Point	264 °C
	MSDS	Chinese USA	Flash Point	197.1±23.6 °C
	Symbol	GHS07, GHS09	Signal Word	Warning

Use of DMXAA (Vadimezan)

Vadimezan (ASA-404; DMXAA), the vascular disrupting agent, is a murine agonist of the stimulator of interferon genes (STING) and also a potent inducer of type I IFNs and other cytokines.

Name	vadimezan
Synonym	More Synonyms

Description	Vadimezan (ASA-404; DMXAA), the vascular disrupting agent, is a murine agonist of the stimulator of interferon genes (STING) and also a potent inducer of type I IFNs and other cytokines.
Related Catalog	Signaling Pathways >> Immunology/Inflammation >> Interleukin Related Signaling Pathways >> Immunology/Inflammation >> STING Research Areas >> Cancer
Target	STING[1], type I IFNs[2]
In Vitro	Vadimezan (DMXAA), the vascular disrupting agent, is a murine agonist of the stimulator of interferon genes (STING) and also a potent inducer of type I IFNs and other cytokines. Vadimezan (DMXAA) has no detrimental effect on 344SQ-ELuc cell viability. It is found that Vadimezan-mediated up regulation of the NF-κB pathway as shown by increased p65 phosphorylation in M2 macrophages[1]. Results demonstrate that Vadimezan (DMXAA)-treated cells are protected from VSV-induced cytotoxicity at all MOIs in contrast to medium-pretreated macrophages. Vadimezan (DMXAA) effectively inhibits growth of both strains of influenza, demonstrating the potential of Vadimezan for treatment of drug-resistant strains of human influenza[2].
In Vivo	344SQ-ELuc NSCLC subcutaneous tumors respond dramatically to Vadimezan (DMXAA), with a marked decrease in bioluminescence (BLI) signals post-drug injection. Vadimezan (DMXAA) treatment of 344SQ-ELuc metastases yields no decrease in photon emission rates, with the tumors remaining histologically similar to controls after this treatment. As with the large subcutaneous tumors, Vadimezan (DMXAA) administration to mice with small subcutaneous tumors still leads to ~2-log decreases in photon emission at both 6 and 24 hours[1]. In vivo, Vadimezan (DMXAA) is a more potent inducer of IFN-β mRNA and a relatively poor inducer of TNF-α mRNA. Vadimezan (DMXAA) administration leads to significantly less weight loss in influenza-infected mice[2].
Kinase Assay	M2-polarized macrophages are treated with 20 µg/mL Vadimezan (ASA-404) or DMSO vehicle for 30 min. Cells are then lysed and protein denatured in SDS buffer and samples sent for RPPA analysis. Differential abundance of various proteins and/or their phosphorylation status in response to Vadimezan (ASA-404) is assessed[1].
Cell Assay	RAW 264.7 macrophages are cultured and plated at 1×105 cells/well in a 96-well plate. After overnight incubation at 37°C, cells are treated with medium containing vehicle or Vadimezan (DMXAA) (100 μg/mL). After 6 h, the culture medium is replaced with serum-free DMEM containing VSV at the indicated MOI for 1 h. Cells are then maintained in complete DMEM with 10% FBS. Twenty-four hours later, cells are washed with PBS, fixed with 10% buffered formalin, and rinsed thoroughly with distilled water. Adherent cells are stained with crystal violet[2].
Animal Admin	Male 129/Sv mice (6 to 12 week old) are used in this study. To generate subcutaneous tumors, 5×105 344SQ-ELuc cells in 100 µL PBS are injected in both posterior flanks of mice. Tumor growth is monitored every 2 to 4 days via BLI. Once tumors are established (day 10 for systemic metastases; day 7 or day 14 for subcutaneous tumors), mice are given 25 mg/kg of Vadimezan (DMXAA), or DMSO vehicle by i.p. injection. BLI is carried out at 6 and 24 hours [1].
References	[1]. Downey CM, et al. DMXAA causes tumor site-specific vascular disruption in murine non-small cell lung cancer, and like the endogenous non-canonical cyclic dinucleotide STING agonist, 2'3'-cGAMP, induces M2 macrophage repolarization. PLoS One. 2014 Jun 18;9(6):e99988. [2]. Shirey KA, et al. The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-beta-mediated antiviral activity in vitro and in vivo. J Leukoc Biol. 2011 Mar;89(3):351-7.

Density	1.3±0.1 g/cm3
Boiling Point	520.9±50.0 °C at 760 mmHg
Melting Point	264 °C
Molecular Formula	C₁₇H₁₄O₄
Molecular Weight	282.291
Flash Point	197.1±23.6 °C
Exact Mass	282.089203
PSA	67.51000
LogP	3.60
Appearance of Characters	solid \| light brown
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.633
Storage condition	2-8°C
Water Solubility	DMSO: 17 mg/mL, soluble

Section1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name: DMXAA
CAS-No.: 117570-53-3
Relevant identified uses of the substance or mixture and uses advised against
Identified uses: Laboratory chemicals, Manufacture of substances

Section2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Acute toxicity, Oral (Category 4)
Acute aquatic toxicity (Category 1)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Harmful if swallowed. Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic
environment.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal wordWarning
Hazard statement(s)
H302Harmful if swallowed.
H400Very toxic to aquatic life.
Precautionary statement(s)
P273Avoid release to the environment.
Supplemental Hazardnone
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R22Harmful if swallowed.
R50/53Very toxic to aquatic organisms, may cause long-term adverse effects in
the aquatic environment.
S-phrase(s)
S60This material and its container must be disposed of as hazardous waste.
S61Avoid release to the environment. Refer to special instructions/ Safety
data sheets.
Other hazards - none

Section3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms: 5,6-Dimethylxanthenone-4-acetic Acid
Formula: C17H14O4 C17H14O4
Molecular Weight: 282,29 g/mol
ComponentConcentration
5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid
CAS-No.117570-53-3-

Section4. FIRST AID MEASURES
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Indication of any immediate medical attention and special treatment needed
no data available

Section5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

Section6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the
environment must be avoided.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

Section7. HANDLING AND STORAGE
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire
protection.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end uses
no data available

Section8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).

Section9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) AppearanceForm: solid
b) Odourno data available
c) Odour Thresholdno data available
d) pHno data available
e) Melting point/freezingno data available
point
f) Initial boiling point and no data available
boiling range
g) Flash pointno data available
h) Evaporation rateno data available
i) Flammability (solid, gas) no data available
j) Upper/lowerno data available
flammability or
explosive limits
k) Vapour pressureno data available
l) Vapour densityno data available
m) Relative densityno data available
n) Water solubilityno data available
o) Partition coefficient: n- log Pow: 3,207
octanol/water
p) Autoignitionno data available
temperature
q) Decompositionno data available
temperature
r) Viscosityno data available
s) Explosive propertiesno data available
t) Oxidizing propertiesno data available
Other safety information
no data available

Section10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

Section11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC:No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
InhalationMay be harmful if inhaled. May cause respiratory tract irritation.
IngestionHarmful if swallowed.
SkinMay be harmful if absorbed through skin. May cause skin irritation.
EyesMay cause eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.
Additional Information
RTECS: ZD5536200

Section12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
Very toxic to aquatic life.
no data available

Section13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed
professional waste disposal service to dispose of this material. Dissolve or mix the material with a
combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

Section14. TRANSPORT INFORMATION
UN number
ADR/RID: 3077IMDG: 3077IATA: 3077
UN proper shipping name
ADR/RID: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (5,6-Dimethyl-9-oxo-9H-
xanthene-4-acetic acid)
IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (5,6-Dimethyl-9-oxo-9H-
xanthene-4-acetic acid)
IATA:Environmentally hazardous substance, solid, n.o.s. (5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic
acid)
Transport hazard class(es)
ADR/RID: 9IMDG: 9IATA: 9
Packaging group
ADR/RID: IIIIMDG: IIIIATA: III
Environmental hazards
ADR/RID: yesIMDG Marine pollutant: yesIATA: yes
Special precautions for user
Further information
EHS-Mark required (ADR 2.2.9.1.10, IMDG code 2.10.3) for single packagings and combination
packagings containing inner packagings with Dangerous Goods > 5L for liquids or > 5kg for solids.

Section15. REGULATORY INFORMATION
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
no data available

Section16. OTHER INFORMATION
Further information
Copyright 2012 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

Symbol	GHS07, GHS09
Signal Word	Warning
Hazard Statements	H302-H400
Precautionary Statements	P273
Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Faceshields;Gloves
Hazard Codes	Xn: Harmful;N: Dangerous for the environment;
Risk Phrases	R22;R50/53
Safety Phrases	60-61
RIDADR	UN 3077
WGK Germany	3
RTECS	ZD5536200
HS Code	2932999099

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