Crenolanib (CP-868596) | FLT3 Inhibitor

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CAS No. :	670220-88-9
Formula :	C₂₆H₂₉N₅O₂
M.W :	443.54
SMILES Code :	NC1CCN(C2=C3N=C(N4C=NC5=CC(OCC6(C)COC6)=CC=C45)C=CC3=CC=C2)CC1
Synonyms :	CP-868596; CP 868,596; ARO 002
MDL No. :	MFCD21609260
InChI Key :	DYNHJHQFHQTFTP-UHFFFAOYSA-N
Pubchem ID :	10366136

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

Primary human hepatic stellate cells (HSC)	1μM		To evaluate the inhibitory effect of Crenolanib on PDGF-BB-induced hepatic stellate cell proliferation	PMC6876711
MOLM-13/sor cells	50 nM	24 h	Crenolanib induced apoptosis in MOLM-13/sor cells by inhibiting FLT3-ITD and Axl signaling pathways, activating GSK3β and downregulating Mcl-1.	PMC9899255
hepatic stellate cells (HSC)	0.1 µM	72 h	Crenolanib significantly inhibited PDGF-BB-mediated HSC proliferation	PMC8067177
hepatic stellate cells (HSC)	1 µM	7 days	Crenolanib treatment induced polygonal cell morphology and lipid accumulation in HSC	PMC8067177
mouse mammary fibroblasts (MMFs)	1 μM	24 h	Inhibition of PDGFRα-D842V mutation significantly diminished Has1 expression in the PDGFRαactivated MMFs, but did not affect Col1a1, Loxl1 and Mmp3.	PMC5440288
Human brain microvascular ECs	5 nM		To study the inhibitory effect of Crenolanib on GBM endothelial cells, results showed that combined use with VEGFR inhibitor Ki8751 inhibited endothelial cell proliferation.	PMC6110798
Healthy control and systemic sclerosis (SSc) dermal fibroblasts	100 nM	24 h	To investigate the effect of Crenolanib on periostin, CCN2, and type I collagen expression in healthy control and SSc dermal fibroblasts. Results showed that Crenolanib significantly reduced periostin and CCN2 protein expression, but had only modest inhibition on type I collagen.	PMC5560111
Healthy control and systemic sclerosis (SSc) dermal fibroblasts	100 nM	30 min	To investigate the effect of Crenolanib on ERK1/2 and Akt phosphorylation in healthy control and SSc dermal fibroblasts. Results showed that Crenolanib effectively inhibited PDGFAA and PDGFBB-induced ERK1/2 and Akt phosphorylation.	PMC5560111

Mice	PDGFR αK mosaic mutant mice	Intraperitoneal injection	15mg/kg	Once daily for 7 days	Crenolanib significantly increased adipogenesis, further supporting the conclusion that PDGFR αK does not erase adipogenic potential.	PMC7214206
NOD-SCID mice	MOLM-13/sor xenograft model	Oral	10 mg/kg	Once daily for 12 days	Crenolanib alone was not effective in the MOLM-13/sor xenograft model, and the combination with HHT did not show improvement.	PMC9899255
rats	thioacetamide (TAA)-induced liver fibrosis model	via drinking water	0.05 mg/L	for 2 weeks	Crenolanib significantly improved recovery from TAA-induced liver fibrosis	PMC8067177
Mice	RCAS transgenic GBM model	Peritoneal injection	50 mg/kg	Not specified	To study the inhibitory effect of Crenolanib on GBM tumor growth, results showed that combined use with Ki8751 significantly prolonged mouse survival and inhibited tumor growth.	PMC6110798
Mice	Ang II-induced skin and heart fibrosis model	Intraperitoneal injection	15 mg/kg	Once daily for 2 weeks	To evaluate the therapeutic effects of Crenolanib in the Ang II-induced skin and heart fibrosis model. Results showed that Crenolanib significantly reduced skin and heart fibrosis.	PMC5560111

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CAS No.: 670220-88-9

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CAS No.: 670220-88-9

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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	2.25mL 0.45mL 0.23mL	11.27mL 2.25mL 1.13mL	22.55mL 4.51mL 2.25mL
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