AZD8186

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CAS No. :	1627494-13-6
Formula :	C₂₄H₂₅F₂N₃O₄
M.W :	457.47
SMILES Code :	O=C(C1=CC(C(C=C(N2CCOCC2)O3)=O)=C3C([C@H](NC4=CC(F)=CC(F)=C4)C)=C1)N(C)C
Synonyms :	AZD8186
InChI Key :	LMJFJIDLEAWOQJ-CQSZACIVSA-N
Pubchem ID :	52913813

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

MDA-MB-468	0.5 µM	1, 3, 6, and 24 hours	To assess the effect of PI3K β inhibition on metabolic pathway activities in a PTEN null breast cancer cell line, the results showed that AZD8186 significantly altered 286 isotope-enriched features, of which 19 features could be attributed to known targeted pathways.	PMC9614656
HCC70	100 nM	14-21 days	To screen for genes conferring resistance to the PI3Kβ inhibitor AZD8186	PMC9652152
EVSA-T	250 nM	14-21 days	To screen for genes conferring resistance to the PI3Kβ inhibitor AZD8186	PMC9652152
ZR-75-1	50 nM	14-21 days	To screen for genes conferring resistance to the PI3Kβ inhibitor AZD8186	PMC9652152
LNCaP	25 nM	2 hours	AZD8186 at 25 nM significantly inhibited Akt phosphorylation in LNCaP cells	PMC4293347
HT	0.5 µM	24 hours	Induced G0/G1 cell cycle arrest	PMC9883168
K422	0.5 µM	24 hours	Induced G0/G1 cell cycle arrest	PMC9883168
KYSE70 cells	3μg/ml, 30μg/ml	24 hours	To evaluate cell apoptosis and cell cycle distribution, results showed AZD8186 induced cell apoptosis and G1 phase arrest.	PMC6648684
MKN45 and MKN28 gastric cancer cells	0, 10, 50, 100, 200, 500 μM	24 hours and 48 hours	To evaluate the inhibitory effect of AZD8186 on gastric cancer cells, the results showed that AZD8186 exhibited a dose-dependent inhibitory effect on MKN45 and MKN28 cells after 24 and 48 hours.	PMC11220201
BT-549	250 nM	30 minutes	AZD8186 at 250 nM significantly inhibited Akt phosphorylation in BT-549 cells within 30 minutes	PMC4293347
OCI-Ly10	0.5 µM	48 hours	Induced apoptosis	PMC9883168
TMD8	0.5 µM	48 hours	Induced apoptosis	PMC9883168
Riva	0.5 µM	48 hours	Induced apoptosis	PMC9883168
A2780	4.88 to 13.39 µM	48 hours	To evaluate the inhibitory effect of AZD8186 on A2780 cells, the results showed that PI3KCA-mutated cells were more sensitive to AZD8186.	PMC7063971
A2780CP70	4.88 to 13.39 µM	48 hours	To evaluate the inhibitory effect of AZD8186 on A2780CP70 cells, the results showed that PI3KCA-mutated cells were more sensitive to AZD8186.	PMC7063971
HAC-2	4.88 to 13.39 µM	48 hours	To evaluate the inhibitory effect of AZD8186 on HAC-2 cells, the results showed that PI3KCA-mutated cells were more sensitive to AZD8186.	PMC7063971
Daoy cells	1 µM	6 hours	Inhibition of PI3K/AKT/mTOR signaling pathway, detection of SOX9 protein degradation	PMC5069553
DU145-DR	5 µM	72 h	AZD8186 alone strongly suppressed AKT and GSK3 β phosphorylation and, to a lesser degree, S6 phosphorylation.	PMC10838968
PC3-DR	5 µM	72 h	AZD8186 alone strongly suppressed AKT and GSK3 β phosphorylation and, to a lesser degree, S6 phosphorylation.	PMC10838968
BT-474	250 nM		AZD8186 at 250 nM had no significant effect on Akt/mTOR signaling in BT-474 cells	PMC4293347
HNSCC cells	1.5 µM		AZD8186 enhances radio- and radiochemosensitivity in the majority of HNSCC cell models, independent of PIK3CA mutation status	PMC11627550

Mice	LNCaP xenograft model	EC50	75 mg/kg	Single dose	AZD8186 at a single dose of 75 mg/kg significantly inhibited Akt signaling in the LNCaP xenograft model, but the signaling rebounded after 8 hours	PMC4293347
Mice	OCI-Ly10 and K422 xenograft models		50 mg/kg	Daily, for 35 days	Combination of AZD8186 and AZD2014 significantly reduced tumor growth	PMC9883168
Nude mice	HCC70 and PC3 xenograft models	Oral	25 mg/kg or 50 mg/kg	Single dose or every 12 hours for 1 week	To evaluate the inhibitory effects of AZD8186 on AKT and rpS6 phosphorylation. In the HCC70 xenograft model, AZD8186 suppressed phosphorylation of AKT1, AKT2, and rpS6 for 4 to 7 hours post-single dose, but levels returned to baseline by 24 hours. In the PC3 xenograft model, AZD8186 suppressed phosphorylation of AKT3 at all doses tested.	PMC8026683
BALB/c (nu/nu) mice	DU145-DR xenograft model	Oral	40 mg/kg	Twice daily for 18 days	The combination of AZD8186 with selumetinib significantly reduced tumor growth without showing toxicity.	PMC10838968
Nude-Foxn1nu mice	HCC70 tumor xenograft model	Oral	66.6 mg/kg	Once daily for 7 days	To evaluate the anti-tumor activity of AZD8186 in combination with AZD5991	PMC9652152
Nude mice	KYSE70 esophageal cancer xenograft model	tail vein injection	10mg/kg	every three days for 21 days	To evaluate the anti-tumor efficacy of AZD8186-DCM and DTX-DCM combination therapy, results showed that the combination therapy significantly inhibited tumor growth.	PMC6648684
NOD/SCID mice	NOD/SCID mice	Oral	25 or 50 mg/kg	twice daily, 5 days on, 2 days off	To evaluate the inhibitory effect of AZD8186 on tumor growth in mice, the results showed that AZD8186 significantly inhibited the growth of ES2 tumors.	PMC7063971

CAS No.: 1627494-13-6

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Precautionary Statements-General

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Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	2.19mL 0.44mL 0.22mL	10.93mL 2.19mL 1.09mL	21.86mL 4.37mL 2.19mL
Dissolving Methods	Animal experiment Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn: in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day; 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 Protocol 2

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