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BMS-309403

Names

[ CAS No. ]:
300657-03-8

[ Name ]:
BMS-309403

[Synonym ]:
Acetic acid, 2-[[2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)[1,1'-biphenyl]-3-yl]oxy]-
{[2'-(5-Ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-3-biphenylyl]oxy}acetic acid
2-[[2'-(5-Ethyl-3,4-diphenyl-1H-pyrazol-1-yl)[1,1'-biphenyl]-3-yl]oxy]acetic acid
UNII-M5X9XSU6J5
T4B
((2'-(5-Ethyl-3,4-Diphenyl-1h-Pyrazol-1-Yl)-3-Biphenylyl)oxy)acetic Acid
cc-561
[2'-(5-Ethyl-3,4-diphenyl-pyrazol-1-yl)-biphenyl-3-yloxy]acetic acid
BMS-309403

Biological Activity

[Description]:

BMS-309403 is a potent, selective and cell-permeable inhibitor of fatty acid binding protein 4 (FABP4) with a Ki of less than 2 nM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> FABP
Research Areas >> Cardiovascular Disease
Research Areas >> Metabolic Disease

[Target]

Ki: less than 2 nM (FABP4), 250 nM (FABP3), 350 nM (FABP5)[1]


[In Vitro]

BMS-309403 binds to FABP4 with high affinity and shows over 100-fold selectivity against FABP5 as well as the heart isoform FABP3[1]. BMS-309403 interacts with the fatty-acid-binding pocket within the interior of the protein and competitively inhibits the binding of endogenous fatty acids. Treatment with BMS-309403 significantly decreased MCP-1 production from THP-1 macrophages in a dose- and time-dependent manner[2]. BMS-309403 stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent manner via activation of AMP-activated protein kinase (AMPK) signaling pathway but independent of FABPs[3].

[In Vivo]

A 6 week treatment with BMS-309403 improves endothelial function, phosphorylated and total eNOS and reduced plasma triglyceride levels but does not affect endothelium-independent relaxations. In cultured human microvascular endothelial cells, lipid-induced A-FABP expression is associated with reduced phosphorylated eNOS and NO production and is reversed by BMS-309403[4]. The extent of atherosclerotic lesion area in the proximal aorta is significantly reduced in the BMS-309403-treated group compared with vehicle-treated controls in both the early and late intervention studies[2].

[Animal admin]

Mice: To determine the effects of pharmacological inhibition of the actions of A-FABP, either the A-FABP inhibitor BMS-309403 (15 mg/kg) or vehicle (4% Tween 80) are administered chronically by daily oral gavage for 6 weeks in ApoE−/− mice (starting at weeks 12 of age). Mice are anaesthetized with a bolus injection of pentobarbitone sodium (230 mg/kg) and their aorta removed and dissected for further analysis[4].

[References]

[1]. Sulsky R, et al. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP). Bioorg Med Chem Lett. 2007 Jun 15;17(12):3511-5.

[2]. Furuhashi M, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007 Jun 21;447(7147):959-65.

[3]. Lin W, et al. BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase. PLoS One. 2012;7(8):e44570.

[4]. Lee MY, et al. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76.


[Related Small Molecules]

HTS01037

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
657.5±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C31H26N2O3

[ Molecular Weight ]:
474.550

[ Flash Point ]:
351.4±31.5 °C

[ Exact Mass ]:
474.194336

[ PSA ]:
64.35000

[ LogP ]:
7.69

[ Vapour Pressure ]:
0.0±2.1 mmHg at 25°C

[ Index of Refraction ]:
1.623

Safety Information

[ Hazard Codes ]:
Xi

Related Compounds