BMS-309403 | FABP4 Inhibitor

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CAS No. :	300657-03-8
Formula :	C₃₁H₂₆N₂O₃
M.W :	474.55
SMILES Code :	O=C(O)COC1=CC(C2=CC=CC=C2N3N=C(C4=CC=CC=C4)C(C5=CC=CC=C5)=C3CC)=CC=C1
Synonyms :	Adipocyte FABP Inhibitor; Fatty Acid Binding Protein 4 Inhibitor; FABP4 Inhibitor
MDL No. :	MFCD09991687
InChI Key :	SJRVJRYZAQYCEE-UHFFFAOYSA-N
Pubchem ID :	16122583

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

DRG neurons	10 µM	15 minutes	BMS309403 inhibited CAY10455 uptake in DRG neurons, reducing AEA uptake	PMC3748184
Human umbilical vein endothelial cells (HUVECs)	20 μM	24 hours	BMS309403 significantly inhibited the tube formation, proliferation, migration, and invasion of HUVECs induced by rhFABP4 or M1-polarized macrophage supernatant.	PMC9213409
Fibroblast-like synoviocytes (FLSs)	20 μM	24 hours	BMS309403 significantly inhibited the proliferation, migration, and invasion of FLSs induced by rhFABP4 or M1-polarized macrophage supernatant.	PMC9213409
SKOV3ip1 cells	20 μM	24 hours	BMS309403 treatment resulted in cell cycle arrest, increasing the number of cells in the G1 phase and reducing the number of cells in the S phase.	PMC10656748
RBE cells	20 μM	24 hours	BMS309403 significantly suppressed the adipose-induced CCA invasion and migration in vitro and reversed the effects of adipose tissue extracts on EMT-related protein expression.	PMC5729422
Hccc-9810 cells	20 μM	24 hours	BMS309403 significantly suppressed the adipose-induced migration and invasion of Hccc-9810 cells.	PMC5729422
Human Microvascular Endothelial Cells (HMECs)	50 µM	24 hours	BMS-309403 reversed the palmitate-induced reduction in eNOS phosphorylation and cGMP production, indicating its beneficial effect on endothelial function.	PMC3057294
HepG2 cells	10, 30, 50 µM	24 hours	BMS309403 reversed the promoting effects of FABP4 on HepG2 cell proliferation and migration, and increased active caspase 3 expression.	PMC6484689
HuH7 cells	10, 30, 50 µM	24 hours	BMS309403 reversed the promoting effects of FABP4 on HuH7 cell proliferation.	PMC6484689
Thp-1 cells	50 µM	24 hours	Inhibition of A-FABP almost reversed PA-induced macrophage apoptosis, indicating that A-FABP plays a critical role in PA-induced macrophage apoptosis.	PMC5797554
BV-2 cells	50 µM	24 hours	To evaluate the effect of BMS309403 on LPS-induced inflammatory response in BV-2 cells, results showed that BMS309403 significantly reduced ROS and TNF-α production.	PMC10577108
Primary mouse microglia	50 µM	24 hours	To evaluate the effect of BMS309403 on LPS-induced inflammatory response in primary mouse microglia, results showed that BMS309403 significantly reduced TNF-α production.	PMC10577108
Mouse renal tubular epithelial cells (TCMK-1)	10 μM	30 minutes	Inhibition of FABP4, alleviating LPS-induced inflammation and apoptosis	PMC9001746
Rat neutrophils	10 μM	30 minutes	After BMS-309403 treatment, FABP4 expression in rat neutrophils decreased, and apoptosis was reduced.	PMC11511807
Mouse neutrophils	10 μM	30 minutes	After BMS-309403 treatment, FABP4 expression in mouse neutrophils decreased, and apoptosis was reduced.	PMC11511807
C1498 cells	30 µM	48 hours	BMS309403 treatment led to downregulation of DNMT1, reduction of global DNA methylation, and restoration of p15INK4B expression	PMC5871544
MV4-11 cells	30 µM	48 hours	BMS309403 treatment led to downregulation of DNMT1, reduction of global DNA methylation, and restoration of p15INK4B expression	PMC5871544
Kasumi-1 cells	30 µM	48 hours	BMS309403 treatment led to downregulation of DNMT1, reduction of global DNA methylation, and restoration of p15INK4B expression	PMC5871544
Bone marrow-derived macrophages (BMDMs)	2.5 ng/ml	5 days	To investigate the role of FABP4 in TGF-b1-induced transition of BMDMs into myofibroblasts, results showed that FABP4 deficiency significantly inhibited TGF-b1-induced a-SMA expression.	PMC7554244
COS-7 cells	20–100 µM	5 minutes	BMS-309403 significantly reduced AEA uptake and hydrolysis in COS-7 cells, with a maximal inhibition of 48%.	PMC2669397
N18TG2 cells	20–100 µM	5 minutes	BMS-309403 significantly reduced AEA uptake and hydrolysis in N18TG2 cells, with a maximal inhibition of 57%.	PMC2669397
PE01 and PE04 cells	20 μM	72 hours	BMS309403 significantly increased the sensitivity of PE04 cells to carboplatin.	PMC10656748

C57BL/6 mice	High-fat diet-induced steatotic liver transplantation model	Intraperitoneal injection	5 mg/kg	Single dose, 1 hour before transplantation	To evaluate the protective effect of BMS-309403 on ischemia-reperfusion injury in the steatotic liver transplantation model, results showed that BMS-309403 reduced hepatocyte apoptosis, decreased serum transaminase levels, and alleviated oxidative stress damage.	PMC10858962
C57BL/6 mice	leukemia model	intraperitoneal injection	5 mg/kg and 10 mg/kg	Initial dose of 5 mg/kg, leukemia cells injected 12 hours later, 3 additional doses within 3 days, followed by two doses of 10 mg/kg	BMS309403 significantly reduced leukemic burden, prolonged survival time, and restored granulocytic differentiation of bone marrow cells	PMC5871544
C57BL/6 J mice	Antigen-induced arthritis (AIA) model	Intraperitoneal injection	5 mg/kg	Twice a week for 4 or 8 weeks	BMS309403 significantly reduced FABP4 expression in synovial M1-polarized macrophages and serum, suppressed synovitis, angiogenesis, and cartilage degradation, thereby alleviating experimental RA progression.	PMC9213409
Mice	syngeneic orthotopic mouse model	Oral	20 mg/kg	six days a week for 4 weeks	BMS309403 significantly reduced metastatic tumor burden and increased tumor sensitivity to carboplatin.	PMC10656748
Mice	Apolipoprotein E-deficient mice (ApoE-/-)	Oral gavage	15 mg/kg/day	Once daily for 6 weeks	BMS-309403 improved endothelium-dependent relaxations, increased phosphorylated and total eNOS levels, and reduced plasma triglyceride levels.	PMC3057294
BALB/c Nude mice	heterotopic and orthotopic xenografted model	intraperitoneal injection	45 mg/kg	twice a week for 3 weeks	BMS309403 significantly reduced tumor growth in heterotopic and orthotopic xenografted models and increased tumor necrosis.	PMC6484689
C57BL/6J mice	CLP or LPS-induced septic acute kidney injury model	Oral	40 mg/kg/d	Once daily for 3 days	Inhibition of FABP4, alleviating septic acute kidney injury	PMC9001746
C57BL/6 mice	Unilateral ureteral obstruction (UUO) model	Oral	40 mg/kg/day	Once daily, during the UUO surgery period	To evaluate the effect of BMS-309403 on UUO-induced kidney fibrosis, the results showed that BMS-309403 significantly attenuated kidney fibrosis and lipid deposition.	PMC8175732
C57BL/6 mice	Cecal ligation and puncture (CLP)-induced sepsis model	Intraperitoneal injection	5 mg/kg	Administered 2 days before modeling	BMS-309403 treatment exacerbated CLP-induced lung injury, while neutrophil depletion alleviated the promotion of ARDS development by BMS-309403.	PMC11511807
C57BL/6J mice	Unilateral ureteral obstruction (UUO) model	Oral	50 mg/kg/day	Once daily for 7 days	To investigate the effect of BMS309403 on attenuating renal fibrosis in the UUO model, results showed that BMS309403 significantly reduced renal interstitial inflammation and fibrosis.	PMC7554244

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CAS No.: 300657-03-8

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CAS No.: 300657-03-8

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Precautionary Statements-General

Prevention

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Preparing Stock Solutions		1mg	5mg	10mg
Preparing Stock Solutions	1 mM 5 mM 10 mM	2.11mL 0.42mL 0.21mL	10.54mL 2.11mL 1.05mL	21.07mL 4.21mL 2.11mL
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