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CAS No. :	116666-63-8
Formula :	C₂₉H₄₀Cl₂FN₃O₃
M.W :	568.55
SMILES Code :	O=C(O[C@@]1(CCN(CCCC2=NC3=CC=CC=C3N2)C)[C@@H](C(C)C)C4=C(C=C(F)C=C4)CC1)COC.[H]Cl.[H]Cl
Synonyms :	Ro 40-5967 dihydrochloride; Mibefradil (dihydrochloride); Posicor
MDL No. :	MFCD00881804
InChI Key :	MTJLQTFHJIHXIX-GDUXWEAWSA-N
Pubchem ID :	60662

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

HEK293 T-REx cells	52.6 μM (Orai1), 14.1 μM (Orai2), 3.8 μM (Orai3)	24-72 hours	To investigate the inhibitory effect of Mibefradil on Orai channels. Results showed Mibefradil dose-dependently inhibited Orai1, Orai2, and Orai3 currents.	Br J Pharmacol. 2019 Oct;176(19):3845-3856
Glioblastoma stem-like cells (GSC)	5 μM	24-48 hours	Mibefradil significantly suppressed HIF1α and HIF2 expressions	Cancer Res. 2017 Jul 1;77(13):3479-3490
Glioblastoma stem-like cells (GSC)	5 μM	48 hours	Mibefradil significantly enhances cell death, with enhanced effects in combination with TMZ	Cancer Res. 2017 Jul 1;77(13):3479-3490
Glioblastoma stem-like cells (GSC)	5 μM	5 days	Mibefradil significantly inhibited cell proliferation and enhanced the inhibition of GSC proliferation by TMZ	Cancer Res. 2017 Jul 1;77(13):3479-3490
Glioblastoma stem-like cells (GSC)	2.5-5 μM	48 hours	Mibefradil significantly inhibited cell growth and enhanced the inhibition of GSC growth by TMZ	Cancer Res. 2017 Jul 1;77(13):3479-3490
HT144 human melanoma cells	7 μM	24 hours	To evaluate the effect of Mibefradil on apoptosis, results showed Mibefradil increased the percentage of apoptotic cells in adaptive cells	Br J Cancer. 2020 Mar;122(7):1023-1036
SK-MEL-28 human melanoma cells	7 μM	24 hours	To evaluate the effect of Mibefradil on apoptosis, results showed Mibefradil increased the percentage of apoptotic cells in adaptive cells	Br J Cancer. 2020 Mar;122(7):1023-1036
A375 human melanoma cells	7 μM	24 hours	To evaluate the effect of Mibefradil on apoptosis, results showed Mibefradil increased the percentage of apoptotic cells in adaptive cells	Br J Cancer. 2020 Mar;122(7):1023-1036
4434 mouse melanoma cells	7 μM	24 hours	To evaluate the effect of Mibefradil on apoptosis, results showed Mibefradil increased the percentage of apoptotic cells in partially reprogrammed cells	Br J Cancer. 2020 Mar;122(7):1023-1036
C790 mouse melanoma cells	7 μM	24 hours	To evaluate the effect of Mibefradil on apoptosis, results showed Mibefradil increased the percentage of apoptotic cells in partially reprogrammed cells	Br J Cancer. 2020 Mar;122(7):1023-1036
Jurkat cells	2-10 μM	48 hours	Mibefradil significantly inhibited the growth of Jurkat cells, mainly by inducing apoptosis.	J Exp Clin Cancer Res. 2015 May 21;34(1):54
MOLT-4 cells	2-10 μM	48 hours	Mibefradil inhibited the proliferation of MOLT-4 cells and induced apoptosis by blocking T-type Ca2+ channels and down-regulating ERK1/2 signaling pathway.	J Exp Clin Cancer Res. 2015 May 21;34(1):54
HK-2 cells	1-25 μM	24 hours	To study the effect of Mibefradil on cell cycle. Results showed low concentrations of Mibefradil increased the percentage of cells at G0/G1 phase, while high concentrations decreased the percentage of cells at S phase and G2/M phase.	Br J Pharmacol. 2019 Oct;176(19):3845-3856
rat primary cortical neurons	10 μM		As a low-voltage–activated (T-type) Ca2+ channel blocker for spatially resolved chemical neuromodulation, it did not effectively block Ca2+ signal propagation	Sci Adv. 2023 Mar 10;9(10):eadf0925
rat afferent arteriole vascular smooth muscle cells	1 μM	10 minutes	To investigate the effect of Mibefradil on Ca2+ entry induced by KCl-induced membrane depolarization. Results showed that Mibefradil did not significantly affect KCl-induced Ca2+ entry.	Hypertension. 2015 Aug;66(2):374-81

Immunodeficient mice	GSC 827-derived glioblastoma murine xenografts	Oral gavage	24 mg/kg	Every 6 hours for 4 days, stopped for 7 days, total two cycles	Mibefradil significantly inhibited tumor growth and prolonged host survival, with additive effects when combined with TMZ	Cancer Res. 2017 Jul 1;77(13):3479-3490
NSG mice	HT144 and A375 xenograft models	Oral	0.25 mg/mL	Once daily for 5 days	To evaluate the effect of Mibefradil on tumor growth, results showed Mibefradil significantly reduced tumor volume and improved survival rate	Br J Cancer. 2020 Mar;122(7):1023-1036

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CAS No.: 116666-63-8

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CAS No.: 116666-63-8

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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