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CAS No. :	1443246-62-5
Formula :	C₁₇H₁₄F₂N₄O
M.W :	328.32
SMILES Code :	O=C(NC1=CC(C)=NN1C2=CC=CC=C2)NC3=CC=C(F)C(F)=C3
Synonyms :	VU 0456810; CID 56642816
MDL No. :	MFCD27977571
InChI Key :	IEKSMUSSYJUQMY-UHFFFAOYSA-N
Pubchem ID :	56642816

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H302-H361-H372-H410
Precautionary Statements:	P201-P264-P280-P301+P330+P331-P312
Class:	9
UN#:	3077
Packing Group:	Ⅲ

Hippocampal neurons	10 μM		ML297 induced inward currents in wild-type hippocampal neurons but no response was observed in Kcnj3−/− neurons.	Br J Pharmacol. 2019 Jul;176(13):2238-2249
Hippocampal neurons	377±70 nM (EC50)		ML297 evoked a concentration-dependent inward current in hippocampal neurons from wild-type mice, but had negligible effects in neurons from Girk1−/−mice.	Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10755-60
HEK293 cells	233 ±38 nM (EC50)		ML297 selectively activates recombinant neuronal GIRK channels containing the GIRK1 subunit in a manner that requires phosphatidylinositol-4,5-bisphosphate (PIP2), but is otherwise distinct from receptor-induced, G-protein –dependent channel activation.	Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10755-60
murine K cells	100 μM	2 hours	ML297 had no effect on basal or IBMX-induced GIP secretion	Br J Pharmacol. 2016 Mar;173(5):888-98
murine L cells	100 μM	2 hours	ML297 significantly reduced glucose-stimulated and IBMX-stimulated GLP-1 secretion	Br J Pharmacol. 2016 Mar;173(5):888-98
lOFC neurons	10 μM	10 minutes	ML297 significantly decreased AP spiking of lOFC neurons, indicating that GIRK channel activation can inhibit neuronal excitability.	Neuropsychopharmacology. 2017 Aug;42(9):1800-1812
hippocampal CA1 neurons	10 μM		ML297 caused hyperpolarization, decreased input resistance, and blocked spontaneous action potentials	Sleep. 2019 Mar 1;42(3):zsy244
hypocretin neurons	5 μM		ML297 caused long-lasting hyperpolarization, decreased input resistance, and blocked spontaneous firing of action potentials	Sleep. 2019 Mar 1;42(3):zsy244
BA principal neurons	10 μM		To evaluate GIRK-dependent currents induced by ML297 in BA principal neurons	J Neurosci. 2021 Jul 7;41(27):5809-5821
vDG granule cells	10 μM		To evaluate GIRK-dependent currents induced by ML297 in vDG granule cells	J Neurosci. 2021 Jul 7;41(27):5809-5821
vCA3 pyramidal neurons	10 μM		To evaluate GIRK-dependent currents induced by ML297 in vCA3 pyramidal neurons	J Neurosci. 2021 Jul 7;41(27):5809-5821

Mice	Stress-induced hyperthermia model	Intraperitoneal injection	30 mg/kg	Single dose, tested after 30 minutes	ML297 dose-dependently reduced stress-induced hyperthermia in mice without affecting baseline body temperature.	Br J Pharmacol. 2019 Jul;176(13):2238-2249
Mice	Wild-type and Girk1−/−mice	Intraperitoneal injection	3, 10, 30, 60 mg/kg	Single dose	ML297 suppressed motor activity at the highest dose (60 mg/kg), but lower doses (3, 10, 30 mg/kg) had no impact. ML297 at 30 mg/kg significantly reduced anxiety-related behavior without sedative or addictive effects. The anxiolytic effect of ML297 was lost in Girk1?/?mice.	Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10755-60
Mice	Fmr1—/y mouse model	Intraperitoneal injection	30 mg/kg	Single administration, recorded for 24 hours	ML297 partially reversed the reduced NREM sleep and fragmented architecture in Fmr1—/y mice, improved sleep EEG oscillations, and EEG coherence between cortical areas. Additionally, ML297 administration following contextual fear or spatial learning rescued disrupted memory consolidation in Fmr1—/y mice.	Cell Rep. 2024 Jun 25;43(6):114266
Mice	Chronic unpredictable stress (CUS) model	Systemic injection	20 mg/kg	Single administration	ML297 rescued stress-induced deficits in cognitive flexibility in male mice.	Neuropsychopharmacology. 2021 Nov;46(12):2158-2169
Mice	Grin1 mutant mice	Intraperitoneal injection	30 mg/kg	Single dose, 30 minutes pretreatment	Pretreatment with ML297 significantly reduced the cumulative numbers of spontaneous LFP activities in Grin1 mutant mice following acoustic stimulation, indicating suppression of 5-HT2AR-mediated cortical hyper-excitability via GIRK channel activation.	Transl Psychiatry. 2022 Apr 22;12(1):168
Mice	Contextual fear conditioning (CFC) model	Intraperitoneal injection	30 mg/kg	Single dose, observed for 24 hours	ML297 restored REM sleep post-CFC, improved fear memory consolidation, and increased hippocampal neuron activation during memory recall	Sleep. 2023 Mar 9;46(3):zsac301
Mice		Intraperitoneal injection	30 mg/kg	Once daily for 3 consecutive days	ML297 decreased wakefulness and increased NREM sleep time without altering REM sleep	Sleep. 2019 Mar 1;42(3):zsy244
Female mice	Alcohol dependence model	In vitro electrophysiological recording	10 μM	Single administration	ML297 significantly decreased the excitability of lOFC neurons by activating GIRK channels. Following chronic intermittent ethanol (CIE) exposure, ML297 no longer inhibited neuronal firing.	Neuropharmacology. 2018 Jul 15;137:1-12
Male C57BL/6J mice	EPM test	Intraperitoneal injection	30 mg/kg	Single dose, 30 min before testing	To evaluate the effect of ML297 on avoidance behavior in the EPM test	J Neurosci. 2021 Jul 7;41(27):5809-5821

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CAS No.: 1443246-62-5

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CAS No.: 1443246-62-5

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Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	3.05mL 0.61mL 0.30mL	15.23mL 3.05mL 1.52mL	30.46mL 6.09mL 3.05mL
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