722544-51-6

722544-51-6 structure

Name: Barasertib (AZD1152-HQPA)
Chemical Name: 2-{3-[(7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide
CAS Number: 722544-51-6
Molecular Formula: C₂₆H₃₀FN₇O₃
Molecular Weight: 507.560
Catalog: Biochemical Inhibitor Cell Cycle Aurora Kinase Inhibitor
Create Date: 2018-12-04 14:53:00
Modify Date: 2024-01-04 18:50:02
AZD1152-HQPA is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, and appr 3700 fold more selective for Aurora B over Aurora A.

Name	2-{3-[(7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide
Synonyms	AZD1152-HQPA INH 34 AZD-1152-HQPA 2-{3-[(7-{3-[Ethyl(2-hydroxyethyl)amino]propoxy}-4-quinazolinyl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide Barasertib 2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide 1H-Pyrazole-5-acetamide, 3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)- AZD1152 HPQA

Description	AZD1152-HQPA is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, and appr 3700 fold more selective for Aurora B over Aurora A.
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> Aurora Kinase Signaling Pathways >> Epigenetics >> Aurora Kinase Research Areas >> Cancer
Target	Aurora B:0.37 nM (IC50)
In Vitro	AZD1152 displays >3000-fold selectivity for Aurora B as compared with Aurora A which has an IC50 of 1.368 μM. AZD1152 has even less activity against 50 other serine-threonine and tyrosine kinases including FLT3, JAK2, and Abl. AZD1152 inhibits the proliferation of hematopoietic malignant cells such as HL-60, NB4, MOLM13, PALL-1, PALL-2, MV4-11, EOL-1, THP-1, and K562 cells with IC50 of 3-40 nM, displaying appr 100-fold potency than another Aurora kinase inhibitor ZM334739 which has IC50 of 3-30 μM. AZD1152 inhibits the clonogenic growth of MOLM13 and MV4-11 cells with IC50 of 1 nM and 2.8 nM, respectively, as well as the freshly isolated imatinib-resistant leukemia cells with IC50 values of 1-3 nM, more significantly compared with bone marrow mononuclear cells with IC50 values of >10 nM. AZD1152 induces accumulation of cells with 4N/8N DNA content, followed by apoptosis in a dose- and time-dependent manner[2]. AZD1152-HQPA treatment induces defective cell survival, polyploidy, and cell death in LNCaP cell line. AZD1152-HQPA also decreases expression of AR[3].
In Vivo	AZD1152 (10-150 mg/kg/day) significantly inhibits the growth of a variety of human solid tumor xenografts, including colon, breast, and lung cancers, in a dose-dependent manner[1]. Administration of AZD1152 (25 mg/kg) alone markedly suppresses the growth of MOLM13 xenografts, confirmed by the observation of necrotic tissue with infiltration of phagocytic cells[2].
Cell Assay	Cells are exposed to various concentrations of AZD1152 for 24 or 48 hours. Cell proliferation is measured by 3H-thymidine uptake (isotope added 6 hours before harvest), and the concentration that induced 50% growth inhibition (IC50) is calculated from dose-response curves. Cell cycle analysis is performed by flow cytometry. Cell apoptosis is measured by annexin V–FITC apoptosis detection kit.
Animal Admin	Human tumor xenografts are established by s.c. injecting 100 to 200 μL tumor cells (between 1×106 and 1×107 cells mixed 50:50 with Matrigel) on the flank. Animals are randomized into treatment groups (n=8-11 per group) when tumors reach a defined palpable size (0.2-0.3 cm3 and 0.5-1 cm3 for mice and rats, respectively). AZD1152 is prepared in Tris buffer (pH 9) and administered either as a bolus injection (i.v. or i.p.) or as a continuous 48-h infusion via s.c. implanted osmotic mini-pumps (two 24-h pumps implanted sequentially) in accordance with the manufacturer's instructions. Tumors are measured up to three times weekly with calipers, tumor volumes are calculated, and the data are plotted using the geometric mean for each group versus time. Tumor volume and tumor growth inhibition are calculated. Statistical analysis of any change in tumor volume is carried out using a Student's one-tailed t test (P value of <0.05 is considered to be statistically significant).
References	[1]. Wilkinson RW, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007 Jun 15;13(12):3682-8. [2]. Yang, Jing., et al. AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood. 2007 Sep 15;110(6):2034-40. [3]. Zekri A, et al. AZD1152-HQPA induces growth arrest and apoptosis in androgen-dependent prostate cancer cell line (LNCaP) via producing aneugenic micronuclei and polyploidy. Tumour Biol. 2015 Feb;36(2):623-32.

Density	1.4±0.1 g/cm3
Boiling Point	796.7±60.0 °C at 760 mmHg
Molecular Formula	C₂₆H₃₀FN₇O₃
Molecular Weight	507.560
Flash Point	435.6±32.9 °C
Exact Mass	507.239410
PSA	128.29000
LogP	2.82
Appearance	white to beige
Vapour Pressure	0.0±2.9 mmHg at 25°C
Index of Refraction	1.677
Storage condition	2-8°C
Water Solubility	DMSO: >15mg/mL

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name: AZD1152-HQPA
: SML0268
REACH No.: A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not

require a registration or the registration is envisaged for a later
registration deadline.
CAS-No.: 722544-51-6

SECTION 2: Hazards identification
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
This substance is not classified as dangerous according to Directive 67/548/EEC.
Other hazards - none

SECTION 3: Composition/information on ingredients
Substances
Synonyms: 3-[[7-[3-[Ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-
fluorophenyl)-1H-pyrazole-5-acetamide
Formula: C26H30FN7O3
Molecular Weight: 507,56 g/mol
CAS-No.: 722544-51-6
No components need to be disclosed according to the applicable regulations.

SECTION 4: 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
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
no data available

SECTION 5: 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, nitrogen oxides (NOx), Hydrogen fluoride
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Avoid
breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
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.

SECTION 7: Handling and storage
Precautions for safe handling
Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
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 use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

SECTION 8: 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
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
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and
approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

SECTION 9: 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) Evapouration 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- no data available
octanol/water
p) Auto-ignitionno 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

SECTION 10: Stability and reactivity
Reactivity
no data available
Chemical stability
Stable under recommended storage conditions.
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
In the event of fire: see section 5

SECTION 11: 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 sensitisation
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
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

SECTION 12: 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
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
no data available

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. 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.

SECTION 14: Transport information
UN number
ADR/RID: -IMDG: -IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA:Not dangerous goods
Transport hazard class(es)
ADR/RID: -IMDG: -IATA: -
Packaging group
ADR/RID: -IMDG: -IATA: -
Environmental hazards
ADR/RID: noIMDG Marine pollutant: noIATA: no
Special precautions for user
no data available

SECTION 15: 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

SECTION 16 - ADDITIONAL INFORMATION
N/A