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CAS No. :	2230820-11-6
Formula :	C₁₈H₂₀N₈O₂
M.W :	380.40
SMILES Code :	O=C1N(C)C2=CN=C(NC3=CN4C(C=C3C)=NC=N4)N=C2N1C5CCOCC5
MDL No. :	MFCD32062688
InChI Key :	XISVSTPEXYIKJL-UHFFFAOYSA-N
Pubchem ID :	135151360

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

HeLa cells	1 mM	1 hour	To study the binding mode of AZD-7648 with DNA-PKcs, revealing its mechanism of competitive inhibition of ATP binding	Nature. 2022 Jan;601(7894):643-648.
A549 non-small cell lung cancer cells	0.6 nM	1 hour	Evaluate the inhibitory effect of AZD7648 on DNA-PKcs autophosphorylation	Nat Commun. 2019 Nov 7;10(1):5065.
OAW42 ovarian cancer cells	3 µM	16 hours	Evaluate the effect of AZD7648 in combination with doxorubicin on DNA damage and apoptosis	Nat Commun. 2019 Nov 7;10(1):5065.
HNSCC cell lines (FaDu, A253, Detroit 562, UMSCC12, UMSCC74A, UMSCC6)	1 µM	1-hour pretreatment	AZD-7648 significantly reduced clonogenic survival of HNSCC cell lines, particularly following X-ray and proton beam therapy. DER (dose enhancement ratio) ranged from 1.41–2.86 (X-rays) and 1.63–2.52 (proton beam).	Cell Death Discov. 2024 Jun 12;10(1):282.
MC38 cells	1 µM	24 hours	To evaluate the radiosensitizing effect of AZD7648 on MC38 cells. Results showed that AZD7648 at 1 μmol/L significantly enhanced IR-induced cell death, with a DEF37 of 2.02.	Clin Cancer Res. 2021 Aug 1;27(15):4353-4366.
HSPCs (hematopoietic stem and progenitor cells)	7 µM	24 hours	Enhance HDR editing efficiency, reduce NHEJ, and increase the conversion rate of -175T>C and -158C>T in HSPCs	Stem Cell Res Ther. 2024 Dec 31;15(1):504.
Human airway basal stem cells (ABCs)	0.5 µM	24 hours	To evaluate the effect of AZD7648 on gene insertion efficiency, results showed AZD7648 significantly improved gene insertion efficiency (from 34.8% to 61.3%)	Mol Ther Nucleic Acids. 2024 Sep 16;35(4):102339.
UM-SCC-47	5 µM	24 hours	Evaluate the radiosensitizing effect of AZD7648 on HPV+ HNSCC cells, showing significant increase in G2/M arrest and cell death.	Cells. 2024 Feb 6;13(4):304.
CAL33	5 µM	24 hours	Evaluate the radiosensitizing effect of AZD7648 on HNSCC cells, showing significant inhibition of IR-induced DNA double-strand break repair and increased cell death.	Cells. 2024 Feb 6;13(4):304.
Cal78	1, 3, 10 µM	24 hours	Pretreatment with AZD7648 significantly enhanced the inhibitory effect of X-ray and carbon ion irradiation on cell proliferation, leading to G2/M phase cell cycle arrest.	Int J Mol Sci. 2024 Jun 4;25(11):6179.
SW-1353	1, 3, 10 µM	24 hours	Pretreatment with AZD7648 significantly enhanced the inhibitory effect of X-ray and carbon ion irradiation on cell proliferation, leading to G2/M phase cell cycle arrest.	Int J Mol Sci. 2024 Jun 4;25(11):6179.
HEL	50-200 µM	24-72 hours	To evaluate the effect of AZD-7648 on HEL cell density and viability. Results showed IC50 between 150-200 µM after 24 hours, decreasing to 97.7 µM and 85.5 µM after 48 and 72 hours, respectively.	Int J Mol Sci. 2023 Oct 18;24(20):15331.
LAMA-84	100-200 µM	24-72 hours	To evaluate the effect of AZD-7648 on LAMA-84 cell density and viability. Results showed IC50 values of 92.6 µM and 81.6 µM after 48 and 72 hours, respectively.	Int J Mol Sci. 2023 Oct 18;24(20):15331.
K-562	10-200 µM	24-72 hours	To evaluate the effect of AZD-7648 on K-562 cell density and viability. Results showed that IC50 was not reached (IC50 > 200 µM) within the tested concentration range.	Int J Mol Sci. 2023 Oct 18;24(20):15331.
Primary human CD4+ T cells	1 µM	3 days	Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency	Nat Commun. 2023 Aug 14;14(1):4761.
HiPSC	1 µM	3 days	Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency	Nat Commun. 2023 Aug 14;14(1):4761.
HepG2	1 µM	3 days	Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency	Nat Commun. 2023 Aug 14;14(1):4761.
Jurkat	1 µM	3 days	Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency	Nat Commun. 2023 Aug 14;14(1):4761.
HEK293T	1 µM	3 days	Evaluate the effect of AZD7648 on CRISPR/Cas9-mediated HDR-KI efficiency, results showed significant increase in HDR-KI efficiency	Nat Commun. 2023 Aug 14;14(1):4761.
Mature B-cell lines (3301015, 5680001)	1-20 µM	3 days	Evaluate AZD7648 effects on normal B-cell viability; results showed AZD7648 decreased viability of one or both B-cell lines at 1-20μM	Front Cell Dev Biol. 2023 Mar 31;11:1134121.
B-ALL cell lines (LAX56, BLQ5, LAX7R)	1-20 µM	3 days	Evaluate AZD7648 effects on B-ALL cell viability; results showed AZD7648 decreased viability at all tested concentrations	Front Cell Dev Biol. 2023 Mar 31;11:1134121.
MG63 cells	10 µM	48 hours	Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells.	Cancer Res. 2024 Sep 4;84(17):2873-2887.
U2OS cells	10 µM	48 hours	Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells.	Cancer Res. 2024 Sep 4;84(17):2873-2887.
HOS cells	10 µM	48 hours	Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells.	Cancer Res. 2024 Sep 4;84(17):2873-2887.
143B cells	10 µM	48 hours	Evaluate the synergistic effect of AZD-7648 with DOX, results showed AZD-7648 significantly enhanced the inhibitory effect of DOX on osteosarcoma cells.	Cancer Res. 2024 Sep 4;84(17):2873-2887.
Primary human hematopoietic stem and progenitor cells (HSPCs)	0.5 µM	48 hours	Improving homology-directed repair (HDR) efficiency, achieving mean editing efficiency of 97%	Elife. 2024 Jun 3;12:RP91288.
Healthy fibroblasts (SBLF8, SBLF9)	5000 nM	48 hours	AZD7648 alone had minimal toxicity to healthy fibroblasts, but combined with ionizing radiation reduced clonogenic survival	Int J Mol Sci. 2024 May 22;25(11):5629.
HNSCC cell lines (Cal33)	5000 nM	48 hours	AZD7648 combined with ionizing radiation significantly increased cell death with supra-additive effects	Int J Mol Sci. 2024 May 22;25(11):5629.
B2M gene-targeted CD34+ HSPCs	0.33, 1, and 3 µM	48 hours	To evaluate the effect of AZD7648 on NHEJ and HDR, results showed AZD7648 inhibited NHEJ and promoted HDR.	Mol Ther Methods Clin Dev. 2024 Jul 27;32(3):101297.
CD34+ hematopoietic stem and progenitor cells (HSPCs)	0.33, 1, and 3 µM	48 hours	To evaluate the effect of AZD7648 on HDR efficiency, results showed AZD7648 significantly increased HDR efficiency.	Mol Ther Methods Clin Dev. 2024 Jul 27;32(3):101297.
KG-1	100-200 µM	48-72 hours	To evaluate the effect of AZD-7648 on KG-1 cell density and viability. Results showed IC50 of 159.9 µM after 72 hours.	Int J Mol Sci. 2023 Oct 18;24(20):15331.
GOT1	1 µM	5 days	To evaluate the effect of AZD7648 on PRRT-induced cell death, results showed that AZD7648 significantly increased PRRT-induced cell death.	Theranostics. 2023 May 21;13(10):3117-3130.
NCI-H69	1 µM	7 days	To evaluate the effect of AZD7648 on the viability of PRRT-treated cells, results showed that AZD7648 significantly reduced the viability of PRRT-treated cells.	Theranostics. 2023 May 21;13(10):3117-3130.
BON1-SSTR2	1 µM	7 days	To evaluate the effect of AZD7648 on the viability of PRRT-treated cells, results showed that AZD7648 significantly reduced the viability of PRRT-treated cells.	Theranostics. 2023 May 21;13(10):3117-3130.
EW8 cells	0.1 µM	72 hours	AZD-7648 synergized with etoposide, significantly reducing cell viability and proliferation	Mol Cancer Ther. 2024 Aug 1;23(8):1109-1123.
TC-32 cells	0.1 µM	72 hours	AZD-7648 synergized with etoposide, significantly reducing cell viability and proliferation	Mol Cancer Ther. 2024 Aug 1;23(8):1109-1123.
FaDu head and neck cancer cells	0.6 µM	72 hours	Evaluate the effect of AZD7648 in combination with olaparib on genomic instability and apoptosis in ATM-deficient cells	Nat Commun. 2019 Nov 7;10(1):5065.
VMCUB-1	0.01–20 µM	72 hours	To evaluate the radiosensitizing effect of AZD7648 on bladder cancer cells, results showed a decrease in IC50 values with increasing radiation doses	Biomedicines. 2022 May 30;10(6):1277.
J82	0.01–20 µM	72 hours	To evaluate the radiosensitizing effect of AZD7648 on bladder cancer cells, results showed a decrease in IC50 values with increasing radiation doses	Biomedicines. 2022 May 30;10(6):1277.
SCaBER	0.01–20 µM	72 hours	To evaluate the radiosensitizing effect of AZD7648 on bladder cancer cells, results showed a decrease in IC50 values with increasing radiation doses	Biomedicines. 2022 May 30;10(6):1277.

NBSGW mice	Immune-deficient mouse model	Transplant after in vitro treatment	0.3 μM	16 weeks	To evaluate the effect of AZD7648 on long-term engraftment of HDR-edited HSPCs, results showed AZD7648 significantly increased the long-term engraftment of HDR-edited cells.	Mol Ther Methods Clin Dev. 2024 Jul 27;32(3):101297.
Nude mice	A549 xenograft model	Oral	100 mg/kg	Once daily for 21 days	Evaluate the tumor growth inhibitory effect of AZD7648 in combination with radiotherapy	Nat Commun. 2019 Nov 7;10(1):5065.
Rj:NMRI-Foxn1nu/nu mice	BON1-SSTR2 and NCI-H69 xenograft models	Oral gavage	50 mg/kg or 100 mg/kg	Once daily for 7 consecutive days	To evaluate the enhancement of PRRT anti-tumor effects by AZD7648, results showed that AZD7648 significantly enhanced the anti-tumor effects of PRRT.	Theranostics. 2023 May 21;13(10):3117-3130.
NBSGW mice	Β-thalassemia and sickle cell disease model	Tail vein injection	7 μM	Single administration, observed for 16-18 weeks	Enhance HDR editing efficiency, reduce NHEJ, increase the conversion rate of -175T>C and -158C>T in HSPCs, and produce functional HbF in vivo	Stem Cell Res Ther. 2024 Dec 31;15(1):504.
BALB/c nude mice	Subcutaneous xenograft model	Oral	70 mg/kg	Once daily for 14 days	Evaluate the synergistic effect of AZD-7648 with DOX, results showed the combination therapy significantly inhibited osteosarcoma growth.	Cancer Res. 2024 Sep 4;84(17):2873-2887.
Mice	MC38, CT26, and B16-F10 syngeneic tumor models	Oral	75 mg/kg	Once daily for 5 days	To evaluate the antitumor efficacy of AZD7648 in combination with RT. Results showed that the combination of AZD7648 and RT significantly improved tumor control, with complete tumor regressions observed in 75% and 42% of mice in MC38 and CT26 models, respectively.	Clin Cancer Res. 2021 Aug 1;27(15):4353-4366.
Nude mice	TC-32 and EW8 orthotopic xenograft models	AZD-7648 orally, etoposide intraperitoneally	AZD-7648 25 mg/kg BID, etoposide 10 mg/kg daily	Daily for 5 days, repeated every 2 weeks	Combination of AZD-7648 and etoposide led to tumor shrinkage, enhanced DNA damage and apoptosis	Mol Cancer Ther. 2024 Aug 1;23(8):1109-1123.

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CAS No.: 2230820-11-6

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CAS No.: 2230820-11-6

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Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	2.63mL 0.53mL 0.26mL	13.14mL 2.63mL 1.31mL	26.29mL 5.26mL 2.63mL
Dissolving Methods	Animal experiment The prepared working fluid is recommended to be prepared now and used up as soon as possible in a short period of time. The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound. Protocol 1

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