AZD1390 | ATM Inhibitor

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CAS No. :	2089288-03-7
Formula :	C₂₇H₃₂FN₅O₂
M.W :	477.57
SMILES Code :	O=C(N1C(C)C)N(C)C2=C1C3=CC(C4=CC=C(OCCCN5CCCCC5)N=C4)=C(F)C=C3N=C2
MDL No. :	MFCD31619275
InChI Key :	VQSZIPCGAGVRRP-UHFFFAOYSA-N
Pubchem ID :	126689157

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

SF295	100 nM	1 hour	To evaluate the inhibitory effect of AZD1390 on HR and MMEJ, results showed that AZD1390 significantly inhibited HR and MMEJ	PMC11192742
HNSCC cell lines	10 nM	1 hour	To observe the effect of AZD1390 on clonogenic survival of HNSCC cells following X-ray and proton irradiation, results showed that AZD1390 significantly decreased clonogenic survival of HNSCC cell lines.	PMC11169544
3D spheroid HNSCC cells	0.2 µM	1 hour	To observe the effect of AZD1390 on the growth inhibition of 3D spheroid HNSCC cells following X-ray irradiation, results showed that AZD1390 significantly suppressed spheroid growth.	PMC11169544
Panc1 cells	30 nM	3 days	To evaluate the effect of AZD1390 on radiation-induced T1IFN expression, results showed that AZD1390 combined with radiotherapy significantly increased T1IFN reporter activity	PMC11063931
LN18 GBM cells	0-300 nM	4 hours	AZD1390 significantly inhibited ATM autophosphorylation in LN18 GBM cells after 4 hours, indicating its ability to effectively block ATM-dependent DDR pathway.	PMC6010333
A431/CCKBR cells	5 µM	48 hours	AZD1390 inhibits ATM kinase, significantly enhancing the cytotoxicity of 225Ac-PP-F11N on A431/CCKBR cells, reducing cell viability from 14% to 8%.	PMC10241010
SJ-DIPG7 cells	100 nM	6 days	To assess the impact of AZD1390 on radiation-induced DNA damage, results showed that AZD1390 exacerbated DNA damage	PMC10547515
H157	4 μM	6 days	To evaluate the effect of ATM inhibition on Gal-9 expression, results showed a significant increase in Gal-9 levels.	PMC9909994
A549	4 μM	6 days	To evaluate the effect of ATM inhibition on Gal-9 expression, results showed a significant increase in Gal-9 levels.	PMC9909994
B16-F10	10 μM	6 days	To evaluate the effect of ATM inhibition on Gal-9 expression, results showed a significant increase in Gal-9 levels.	PMC9909994
MC-38	10 μM	6 days	To evaluate the effect of ATM inhibition on Gal-9 expression, results showed a significant increase in Gal-9 levels.	PMC9909994
U251 cells	30 nM	6 hours	AZD1390 suppressed radiation-induced ATM signaling, abrogated G0-G1 arrest, and promoted a proapoptotic response specifically in p53-mutant GBM cells.	PMC11064970
GBM12 cells	30 nM	6 hours	AZD1390 suppressed RT-induced ATM signaling in GBM12 cells, exhibiting even greater potency.	PMC11064970
SU-DIPGXIII cells	4 nM	7 days	To evaluate the synergy of AZD1390 with radiation, results showed that AZD1390 significantly enhanced the efficacy of radiation	PMC10547515
KB1P-G3	2 µM	72 hours	AZD1390 inhibits ATM signaling, showing BRCA1-deficient cells are more sensitive to ATM inhibition	PMC9206299
KB1P-B11	2 µM	72 hours	AZD1390 inhibits ATM signaling, showing BRCA1-deficient cells are more sensitive to ATM inhibition	PMC9206299
KP-3.33	2 µM	72 hours	AZD1390 inhibits ATM signaling, showing BRCA1-deficient cells are more sensitive to ATM inhibition	PMC9206299
KP-6.3	2 µM	72 hours	AZD1390 inhibits ATM signaling, showing BRCA1-deficient cells are more sensitive to ATM inhibition	PMC9206299
SU-DIPGXIII ATM KO cells	100 nM		To verify the target specificity of AZD1390, results showed that ATM KO cells did not show further radiosensitization with AZD1390	PMC10547515
SJ-DIPG29 cells	100 nM		To assess the impact of AZD1390 on radiation-induced cytotoxicity, results showed that AZD1390 did not significantly enhance radiation-induced cytotoxicity	PMC10547515
Dorsal Root Ganglion Neurons (DRGN)	1-10 nM		AZD1390 significantly reduced ATM activation levels (pATM levels), with 5 nM being the lowest effective dose, promoting significant increases in DRGN survival, neurite outgrowth, and longest neurite length	PMC9274214

CD-1 Nude mice	SJ-DIPG7 and SJ-DIPG37 orthotopic xenograft models	Oral	20 mg/kg	Once daily for 7 days	To evaluate the tolerability and efficacy of AZD1390 in combination with radiation, results showed that AZD1390 significantly prolonged the survival of mice	PMC10547515
Mice	GBM PDX model	Oral	66 mg/kg	Once daily for 5 days	To evaluate the effect of AZD1390 in combination with TMZ, results showed that AZD1390 significantly enhanced the efficacy of TMZ	PMC11192742
Mice	Patient-derived xenograft (PDX) models	Oral gavage	20 mg/kg/day	Once daily for 4 days	To evaluate the efficacy of AZD1390 combined with radiation therapy in treating breast cancer CNS metastasis. Results showed that pretreatment with AZD1390 followed by radiation significantly inhibited the growth of PDX tumors and improved animal survival.	PMC10618650
Nude mice	Orthotopic GBM xenograft model	Oral	20 mg/kg	Once daily for 5 days	AZD1390 combined with RT significantly prolonged survival in TP53-mutant GBM models, but no significant survival benefit was observed in TP53-WT models.	PMC11064970
Mice	Orthotopic brain tumor model	Oral	20 mg/kg	Once daily for 5 days	AZD1390 combined with daily fractions of IR (whole-brain or stereotactic radiotherapy) significantly induced tumor regressions and increased animal survival compared to IR treatment alone.	PMC6010333
Mice	Spinal Cord Injury Model	Oral	20 mg/kg	Once daily, for 4 weeks	AZD1390 significantly suppressed ATM levels, promoted axon regeneration and functional recovery, and improved sensory and motor function	PMC9274214
BALB/c mice	CT26 subcutaneous tumor model		5 mg/kg	9 times	To evaluate the effect of AZD1390 combined with anti-Gal-9 antibody on tumor growth, results showed that the combination therapy significantly suppressed tumor growth and prolonged survival.	PMC9909994
C57BL/6 mice	Pancreatic cancer model	Oral	20 mg/kg	Once daily for 11 days	To evaluate the antitumor efficacy of AZD1390 in combination with radiotherapy and anti-PD-L1, results showed that the triplet combination significantly inhibited tumor growth and delayed tumor volume doubling	PMC11063931
Mice	BRCA1-deficient mammary tumor model	Oral gavage	20 mg/kg	twice daily for 28 consecutive days	Combination of AZD1390 with GSK126 significantly increased anti-tumor activity and prolonged progression-free survival	PMC9206299

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CAS No.: 2089288-03-7

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CAS No.: 2089288-03-7

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed