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CAS No. :	1037624-75-1
Formula :	C₃₀H₃₄N₈
M.W :	506.64
SMILES Code :	NC1=NC(NC2=CC=C3C(CC[C@@H](N4CCCC4)CC3)=C2)=NN1C5=NN=C6C(CCCC7=CC=CC=C76)=C5
Synonyms :	BGB324; R428; BGB324 (GMP)
MDL No. :	MFCD21608463
InChI Key :	KXMZDGSRSGHMMK-VWLOTQADSA-N
Pubchem ID :	46215462

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

BRAFV600-mutant melanoma short-term cultures	2 μM	4 days	To verify the resistance of MITF-low/NF-κB-high melanoma short-term cultures to RAF and MEK inhibitors.	Cancer Discov. 2014 Jul;4(7):816-27.
BRAFV600-mutant melanoma cell lines	2 μM	4 days	To assess the sensitivity of BRAFV600-mutant melanoma cell lines to the RAF inhibitor PLX4720, finding that MITF-high cell lines were sensitive to PLX4720, while MITF-low/NF-κB-high cell lines were resistant.	Cancer Discov. 2014 Jul;4(7):816-27.
ER3	1.2 μM	16 h	To evaluate the effect of Bemcentinib on autophagic flux in ER3 cells, results showed that Bemcentinib significantly reduced the starvation-induced degradation of long-lived proteins, indicating the blockage of autophagic flux.	J Thorac Oncol. 2020 Jun;15(6):973-999.
HCC827	0.8 μM	24 h	To investigate the effect of Bemcentinib on autophagic flux in HCC827 cells, results showed that Bemcentinib treatment increased the numbers of LC3A/B-positive autophagosomes and lysosomes, indicating the blockage of autophagic flux.	J Thorac Oncol. 2020 Jun;15(6):973-999.
344SQ_Z-cad cells	2 μM	72 h	Bemcentinib specifically killed GFP+ mesenchymal cells, while selumetinib specifically killed RFP+ epithelial cells. Combination treatment significantly increased the total amount of cell death and killed both subpopulations to a greater degree than either single agent.	Cancer Res. 2021 Mar 1;81(5):1398-1412.
MCF-7/ADR cells	1 µM	24 h	To evaluate the inhibitory effect of R428 on Axl activity and its impact on the expression of epithelial and mesenchymal markers in MCF-7/ADR cells. Results showed that R428 significantly inhibited Axl activity and reduced the expression of mesenchymal markers N-cadherin and Vimentin.	Theranostics. 2016 May 24;6(8):1205-19.
BaF3-EpoR-JAK2V617F cells	0.5, 1, 2, 3, 4, 5 µM	48 h	To assess the effect of Bemcentinib on the viability of BaF3-EpoR-JAK2V617F cells, the results showed that Bemcentinib significantly reduced cell viability.	Hemasphere. 2021 Aug 11;5(9):e630.
SET-2 cells	0.5, 1, 2, 3, 4, 5 µM	48 h	To assess the effect of Bemcentinib on the viability of SET-2 cells, the results showed that Bemcentinib significantly reduced cell viability.	Hemasphere. 2021 Aug 11;5(9):e630.
BMDCs	40 nM	24 h	BGB324-treated BMDCs showed increased secretion of IFN-b, indicating that Axl inhibition promotes type I interferon production.	Cell Rep Med. 2022 Mar 15;3(3):100554.
PC9 cells	100 nM	7 days	To assess cell viability, the results showed that Bemcentinib inhibited the viability of PC9 cells.	Cell Rep Med. 2024 Sep 17;5(9):101703.
PC9 cells	100 nM	72 h	To assess cell viability, the results showed that Bemcentinib inhibited the viability of PC9 cells.	Cell Rep Med. 2024 Sep 17;5(9):101703.
Human endometrial stromal cells (hESCs)	1 µM	72 h	Bemcentinib inhibited AXL activation and significantly reduced the expression of Collagen 1 and α-SMA, indicating the importance of the AXL pathway in GAS6 functioning.	EMBO Mol Med. 2023 Sep 11;15(9):e17601.

Nude mice	HCC827 xenograft model	Oral	50 mg/kg or 100 mg/kg	Twice daily for 5 months	To evaluate the effect of Bemcentinib on EGFR inhibitor resistance in the HCC827 xenograft model, results showed that Bemcentinib significantly delayed the onset of tumor resistance to erlotinib.	J Thorac Oncol. 2020 Jun;15(6):973-999.
Mice	344SQ_Z-cad subcutaneous tumor model	Oral	100 mg/kg	Daily for 3-4 weeks	The combination of bemcentinib and selumetinib significantly suppressed tumor growth and had a significant impact on tumor growth throughout the duration of treatment. The combination treatment also significantly reduced the formation of lung metastatic nodules, indicating its inhibitory effect on tumor metastasis.	Cancer Res. 2021 Mar 1;81(5):1398-1412.
BALB/c nude mice	MCF-7/ADR cell subcutaneous xenograft model	Oral	25 mg/kg	Twice daily for 30 days	To evaluate the inhibitory effect of R428 on the growth of MCF-7/ADR cell subcutaneous xenografts. Results showed that R428 significantly inhibited tumor growth and reduced the number of lung metastatic nodules.	Theranostics. 2016 May 24;6(8):1205-19.
NSG mice	SET-2 xenograft model	Oral	50 mg/kg	Twice daily until tumors reached 1500 mm3	To assess the effect of Bemcentinib on tumor growth in the SET-2 xenograft model, the results showed that Bemcentinib significantly inhibited tumor growth.	Hemasphere. 2021 Aug 11;5(9):e630.
Mice	KPL tumor model	Oral	50 mg/kg	Twice daily for 7 days	Combination therapy of BGB324 with anti-PD-1 significantly controlled the growth of KPL tumors and increased the infiltration of TCF1+PD-1+CD8 T cells in the tumor.	Cell Rep Med. 2022 Mar 15;3(3):100554.
Mice	PC9 cell xenograft model	Oral	50 mg/kg	Once daily for 4 weeks	To evaluate the effect of Bemcentinib on tumor relapse, the results showed that Bemcentinib was unable to persistently block relapses.	Cell Rep Med. 2024 Sep 17;5(9):101703.
Mice	NSG mice	Oral	50 mg/kg	Twice daily, continued treatment	To study the effect of Bemcentinib on JAK2 inhibitor resistant mouse models, results showed that Bemcentinib significantly inhibited tumor growth.	Clin Cancer Res. 2024 Feb 1;30(3):586-599.
Mice	IUA mouse model	Oral	80 mg/kg	Started 7 days after the first curettage and continued until the end of the experiment	Bemcentinib significantly ameliorated endometrial fibrosis, reduced collagen deposition, and improved pregnancy outcomes.	EMBO Mol Med. 2023 Sep 11;15(9):e17601.

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CAS No.: 1037624-75-1

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CAS No.: 1037624-75-1

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NCT03824080	Acute Myeloid Leukemia\|High-ri... More >>sk Myelodysplastic Syndrome\|Low-risk Myelodysplastic Syndrome Less <<	PHASE2	COMPLETED	2021-06-08	CHU H?tel Dieu Service d'Hémat... More >>ologie Clinique, Nantes, Nantes Cedex 1, 44093, France\|Service d'Hématologie Séniors, Paris, Paris 7, 75010, France\|H?pital Archet 1 Service d'Hématologie Clinique, Nice, 06200, France\|Universit?tsklinikum Dresden, Dresden, 01307, Germany\|Marien Hospital GmbH, Dusseldorf, Germany\|Universit?tsklinikum Leipzig, Leipzig, 04103, Germany\|Technische Universit?t München, Klinikum rechts der Isar, Munich, Germany\|VU University Medical Center, Amsterdam, 1081 HV, Netherlands Less <<
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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