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CAS No. :	122955-42-4
Formula :	C₂₆H₂₀N₂O
M.W :	376.45
SMILES Code :	O=C1C2=C(C=CC=C2)C(CC3=CC=NC=C3)(CC4=CC=NC=C4)C5=CC=CC=C15
MDL No. :	MFCD09055426

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

CA1 pyramidal neurons	10 µM	10 minutes	To study the effect of XE991 on synaptic transmission in CA1 pyramidal neurons, results showed that XE991 increased the frequency of sEPSCs but did not affect their amplitude.	J Physiol. 2012 Aug 15;590(16):3953-64
Saos-2 cells	10 µM	14 days	XE991 significantly promoted mineralization in Saos-2 cells, while the KV7 opener flupirtine reduced calcium deposits.	Int J Mol Sci. 2016 Mar 18;17(3):407
MG-63 cells	10 µM	14 days	XE991 increased matrix mineralization during osteoblast differentiation by inhibiting KV7.3 channels.	Int J Mol Sci. 2016 Mar 18;17(3):407
CHO cells	10 µM	24 hours	XE991 completely blocked caspase-3 activation induced by KCNQ2/3 channel expression, indicating that inhibition of KCNQ channels can prevent apoptosis.	Cell Death Differ. 2011 Mar;18(3):493-505.
Hippocampal neurons	10 µM	24 hours	XE991 significantly reduced NEM-induced cell death, indicating that inhibition of KCNQ channels can protect neurons from apoptosis.	Cell Death Differ. 2011 Mar;18(3):493-505.
Porcine coronary artery smooth muscle cells	10 µM	30 minutes	To investigate the effect of XE991 on hypoxia-induced vasodilation, results showed that XE991 significantly inhibited hypoxia-induced vasodilation	Br J Pharmacol. 2014 Jan;171(1):69-82
Dorsal root ganglion neurons	10 µM	4 days	To evaluate the effect of XE991 on axonal growth of DRG neurons, results showed XE991 tended to decrease axonal elongation.	Int J Mol Sci. 2024 Jul 3;25(13):7327
Neocortical neurons	1-10 µM	48 hours	To investigate the protective effect of XE991 on C2-ceramide-induced apoptosis, results showed XE991 had no protective effect.	J Neurosci. 2002 Jan 1;22(1):114-22
Rat sympathetic neurons	5 µM	48-72 hours	To investigate the protective effect of XE991 on NGF deprivation-induced apoptosis, results showed XE991 promoted neuronal survival in a concentration-dependent manner.	J Neurosci. 2002 Jan 1;22(1):114-22
Mouse portal vein smooth muscle cells	10 µM	5 minutes	To study the effect of XE991 on membrane potential, results showed XE991 depolarised the resting membrane potential and augmented the evoked response in a concentration-dependent manner.	Br J Pharmacol. 2005 Oct;146(4):585-95
Mouse portal vein smooth muscle cells	5.8 µM (IC50)	5 minutes	To study the inhibitory effect of XE991 on voltage-dependent potassium currents, results showed XE991 inhibited outward current in a concentration-dependent manner with an IC50 of 5.8 μM.	Br J Pharmacol. 2005 Oct;146(4):585-95
HL-1 cells	100 µM	5.5 hours ischemia and 2 hours reperfusion	Evaluate the effect of XE991 on HL-1 cell survival during simulated ischemia/reperfusion, showing cytoprotection when administered during ischemia or throughout the perfusion protocol	Drug Des Devel Ther. 2020 Jul 2;14:2549-2560
Primary rat cortical neurons	10 µM	7 days	XE991 reduced the burden of poly(GA)-EGFP aggregates and increased neuronal activity.	EMBO Mol Med. 2021 Jul 7;13(7):e13131
HiPSC-derived C9orf72-mutant motoneurons	10 µM	7 days	XE991 increased neuronal firing by inhibiting Kv7 channels, reduced aggregate burden, and restored CREB-dependent transcription and synaptic integrity.	EMBO Mol Med. 2021 Jul 7;13(7):e13131

Mice	Rest conditional knockout (cKO) mice	Intraperitoneal injection	0.25 mg/kg and 0.5 mg/kg	Single dose	XE991 partially rescued hearing loss in Rest cKO mice	Elife. 2022 Sep 20;11:e76754
Rat	Isolated perfused rat heart model	Perfusion	10 μM	25 min prior to ischemia and throughout the perfusion protocol	Assess the impact of XE991 on infarct size and hemodynamic recovery, showing reduction in infarct size and improved recovery in all administration groups	Drug Des Devel Ther. 2020 Jul 2;14:2549-2560
Mice	TRPM8-deficient mice	Topical application	10 μM	Not specified	To investigate the effect of XE991 on TRPM8-dependent cold sensing, it was found that XE991 failed to induce cold sensitization in TRPM8-deficient mice.	J Neurosci. 2013 Oct 16;33(42):16627-41
Mice	Freely moving awake mice	Tracheal perfusion	10-30 μM	30 minutes	Pretreatment with XE991 prevented retigabine from abolishing the α,β-MeATP-induced AP firing, indicating that XE991 affected the excitability of mouse lung nodose C-fiber terminals by blocking M-channels.	JCI Insight. 2019 Mar 7;4(5):e124467
Mice	Kv7.2(S559A) knock-in mice	Intraperitoneal injection	2 mg/kg	Single dose	To evaluate the restorative effect of XE991 on long-term object recognition memory in Kv7.2(S559A) mice	J Neurosci. 2020 Jul 22;40(30):5847-5856
Mice	Hot-plate test model in freely moving mice	Intrathalamic injection	2 mM, 300 nL	Single injection, tested 20-60 minutes later	XE991 decreased the pain threshold and reduced the latency of pain-related behavioral responses.	Br J Pharmacol. 2015 Jun;172(12):3126-40
Rats	Inflammatory pain model	Subcutaneous injection	3 mg/kg	Single dose	Investigate the inhibitory effect of XE991 on APAP-induced analgesia	Int J Mol Sci. 2022 Dec 30;24(1):650
Kv1.1-KO mice	Kv1.1 knockout mice	Intraperitoneal injection	5-10 mg/kg	Single dose	XE991 induced bilateral seizure/spreading depolarization complexes and death in Kv1.1-KO mice	Brain. 2021 Oct 22;144(9):2863-2878
Rats	Spontaneously hypertensive rats (SHRs)	Microinjection into the central amygdala (CeA)	6.7 nmol	Single injection, effects lasted approximately 26.8±3.9 minutes	XE-991 increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in WKY rats but had no significant effect in SHRs.	Cardiovasc Res. 2022 Jan 29;118(2):585-596
Borderline hypertensive rats (BHRs)	Chronic unpredictable stress (CUS) model	Bilateral CeA microinjection	6.7 nmol (in 50 nl aCSF into each side)	Single injection	XE-991 increased sympathetic outflow and blood pressure in unstressed BHRs but not in CUS-treated BHRs.	Cardiovasc Res. 2023 Jul 6;119(8):1751-1762

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CAS No.: 122955-42-4

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CAS No.: 122955-42-4

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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