300657-03-8 Usage
Description
2''-(5-ETHYL-3,4-DIPHENYL-PYRAZOL-1-YL)-BIPHENYL-3-YLOXY]ACETIC ACID, also known as BMS 309403, is a potent and selective inhibitor of Fatty Acid Binding Protein 4 (FABP4), specifically designed to target the fatty acid-binding pocket of adipocyte FABP (A-FABP). It exhibits high affinity for FABP4 with a Ki value of less than 2 nM, while showing lower affinity for muscle and epidermal FABP's (Ki values of 250 nM and 350 nM, respectively). BMS 309403 is a cell-permeable biphenylazolo-oxyacetate that has been found to decrease fatty acid uptake in adipocytes in vitro and has demonstrated potential benefits in reducing atherosclerotic lesion area, blood glucose levels, and increasing insulin sensitivity in mouse models.
Uses
Used in Pharmaceutical Industry:
2''-(5-ETHYL-3,4-DIPHENYL-PYRAZOL-1-YL)-BIPHENYL-3-YLOXY]ACETIC ACID is used as a FABP4 inhibitor for targeting the fatty acid-binding pocket of A-FABP, which can potentially lead to the development of novel therapeutics for obesity, atherosclerosis, and related metabolic disorders.
Used in Research Applications:
In the field of research, 2''-(5-ETHYL-3,4-DIPHENYL-PYRAZOL-1-YL)-BIPHENYL-3-YLOXY]ACETIC ACID serves as a valuable tool for studying the role of FABP4 in various biological processes and its potential as a therapeutic target for metabolic diseases.
Used in Drug Development:
2''-(5-ETHYL-3,4-DIPHENYL-PYRAZOL-1-YL)-BIPHENYL-3-YLOXY]ACETIC ACID is used as a lead compound in the development of new drugs aimed at treating obesity, atherosclerosis, and improving insulin sensitivity by inhibiting FABP4.
in vivo
BMS-309403 sodium (15 mg/kg; chronic treatment; daily for 6 weeks) improves endothelial function, phosphorylated and total eNOS and reduced plasma triglyceride levels but did not affect endothelium-independent relaxations
Biochem/physiol Actions
BMS-309403 is a potent and selective inhibitor of fatty acid binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP, aP2). FABP4 is an intracellular lipid-binding protein responsible for the transportation of fatty acids. It is expressed primarily in adipose tissue and is associated with inflammation, obesity, diabetes and cardiovascular diseases. BMS309403 interacts with the fatty-acid-binding pocket within the interior of FABP4 and has been shown to competitively inhibit fatty acid binding with a Ki value < 2 nM. BMS309403 is orally active and has been shown to reduce atherosclerosis in mice studies.
in vitro
Treatment with BMS-309403 significantly decreased MCP-1 production from THP-1 macrophages in a dose- and time-dependent manner.
References
1) Furuhashi?et al.?(2007),?Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2; Nature?447?959
2) Sulsky?et al. (2007),?Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP); Bioorg. Med. Chem. Lett.,?17?3511
3) Lin?et al.?(2012),?BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase; PLoS One,?7?e44570
4) Bosquet?et al.?(2018),?FABP4 inhibitor BMS3409403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation; Biochim. Biophys. Acta Mol. Cell Biol. Lipids,?1863?604
5) Gongl?et al. (2018),?FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury; Biochem. Biophys. Res. Commun.,?496?1115
Check Digit Verification of cas no
The CAS Registry Mumber 300657-03-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,0,0,6,5 and 7 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 300657-03:
(8*3)+(7*0)+(6*0)+(5*6)+(4*5)+(3*7)+(2*0)+(1*3)=98
98 % 10 = 8
So 300657-03-8 is a valid CAS Registry Number.
