Verdinexor (KPT-335) | CRM1 Inhibitor

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CAS No. :	1392136-43-4
Formula :	C₁₈H₁₂F₆N₆O
M.W :	442.32
SMILES Code :	O=C(NNC1=NC=CC=C1)/C=C\N2N=C(C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)N=C2
Synonyms :	KPT-335; ATG-527
MDL No. :	MFCD28167840
InChI Key :	OPAKEJZFFCECPN-XQRVVYSFSA-N
Pubchem ID :	71492799

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

Description	Verdinexor (KPT-335) is an innovative, orally-administered selective inhibitor of nuclear export (SINE) that blocks the nuclear export protein Exportin 1 (XPO1/CRM1), showing efficacy against canine cancer cell lines[1].
Target	CRM1

KYSE510	20 μM	48 hours	To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells	PMC8692140
KYSE180	20 μM	48 hours	To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells	PMC8692140
KYSE450	20 μM	48 hours	To evaluate the inhibitory effect of Verdinexor on the proliferation of esophageal cancer cells	PMC8692140
KYSE30	20 μM	48 hours	To evaluate the independent cytotoxic effect of AZD1775 on esophageal cancer cell lines. AZD1775 (100 nM) as monotherapy did not alter the viability of ESCA cells, but significantly radiosensitized ESCA cells.	PMC8692140
SH-SY5Y	0.3 µM	48 hours	To evaluate the inhibitory effect of Verdinexor on neuroblastoma cell proliferation. Results showed that Verdinexor significantly inhibited the proliferation of SH-SY5Y cells and induced apoptosis.	PMC8359549
SK-N-BE(2)	1.4 µM	48 hours	To investigate the effect of ATR inhibition on RA-induced differentiation of neuroblastoma cells, results showed low-dose elimusertib significantly enhanced RA-induced neuronal differentiation.	PMC8359549
Bone marrow mononuclear cells (BMMC)	0.01 μM, 0.05 μM, 0.1 μM, 0.5 μM, 1 μM, 10 μM	24 hours-4 days	To evaluate the effect of Verdinexor on the survival of plasma cells in bone marrow and blood. Results showed that bone marrow-derived plasma cells were less sensitive to Verdinexor compared to those from blood.	PMC11757124
293T cells	1 μM	6 hours		PMC4136318
MDCK cells	1 μM	2 hours	Evaluate the inhibitory effect of GA-A on cyst growth in MDCK cells, showing significant inhibition without cytotoxicity.	PMC4136318
A549 cells	1 μM	2 hours	Inhibited RSK4 activation, resulting in decreased cellular cIAP1 and cIAP2 expression	PMC4136318
BEAS-2B cells	1 μM	24 hours	To evaluate the effects of Licochalcone A on oxidative responses and inflammatory cytokine levels. Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells.	PMC6364025
VeroE6 cells	0.1 µM	4 days	To evaluate the inhibitory effect of Verdinexor on SARS-CoV-2 replication, results showed that 0.1 µM Verdinexor reduced viral replication by approximately 15%.	PMC9168989
Mouse embryonic fibroblasts (MEFs)	2.5μM	2 hours		PMC5130180
Vero cells	2.5μM	2 hours		PMC5130180
A549 cells	0.2μM	2 hours	Inhibited RSK4 activation, resulting in decreased cellular cIAP1 and cIAP2 expression	PMC5125695

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CAS No.: 1392136-43-4

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CAS No.: 1392136-43-4

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Nude mice	KYSE30 xenograft model	5 mg/kg	Intraperitoneal injection	24 days	To evaluate the inhibitory effect of Verdinexor on tumor growth of esophageal cancer in vivo	PMC8692140
Nude mice	Neuroblastoma xenograft model	10 mg/kg	Oral gavage	Three times per week for four weeks	To evaluate the antitumor effects of Verdinexor in vivo. Results showed that Verdinexor significantly inhibited tumor growth without causing obvious toxic effects.	PMC8359549
BALB/c mice	Influenza virus infection model	10 or 20 mg/kg	Oral	Once daily for 3 days	To evaluate the antiviral effect of Verdinexor in vivo, results showed that Verdinexor reduced lung viral loads, decreased inflammatory responses, and improved survival rates	PMC4136318
Adult Sprague-Dawley rats	Controlled cortical impact (CCI) model of TBI	5 mg/kg or 7 mg/kg	oral	Starting at 2 h post-TBI and once a day thereafter over the next 4 days	To evaluate the effects of SINE compounds on TBI-induced behavioral and histological deficits. Results showed that rats treated with KPT-350 exhibited significantly better motor coordination and balance in the rotorod test and motor asymmetry test, with improvements of 100–200%, observed as early as 4 h after initial SINE compound injection and sustained throughout the 18-day post-TBI study period (P<0.05). Additionally, KPT-350 reduced cortical core impact area and peri-impact cell death (P<0.05).	PMC5067638
Mice	Influenza virus infection model	20 mg/kg	Oral	Once on day 1 and day 3 post-infection	To evaluate the inhibitory effect of Verdinexor on influenza virus replication in vivo, results showed that Verdinexor significantly reduced virus shedding and pulmonary inflammatory response	PMC5125695

Bio Calculators
Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	2.26mL 0.45mL 0.23mL	11.30mL 2.26mL 1.13mL	22.61mL 4.52mL 2.26mL
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