Item no. |
S2694-5 |
Manufacturer |
Selleckchem
|
CASRN |
629664-81-9 |
Amount |
5 mg |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
Fxr 450 , FXR;FXR |
Similar products |
WAY-362450 |
Available |
|
Chemical Name |
(E)-isopropyl 3-(3, 4-difluorobenzoyl)-1, 1-dimethyl-1, 2, 3, 6-tetrahydroazepino[4, 5-b]indole-5-carboxylate |
Clinical Trials |
WAY-362450 is currently on Phase I clinical trials, to examine safety, tolerability, and pharmacokinetics of WAY-362450 administered orally to healthy Japanese male subjects. |
Description |
WAY-362450 is a potent, selective FXR agonist with EC50 of 4 nM. |
IC50 |
4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1] |
In vitro |
WAY-362450 binds to the ligand-binding domain (LBD) of human FXR., WAY-362450 resides in a predominately hydrophobic pocket with only a few polar atoms making contact with WAY-362450. WAY-362450 promotes transcription of the human BSEP, human SHP, and mouse IBABP genes utilizing reporter constructs with EC50 of 17, 230, and 33 nM, respectively in promoter assays. WAY-362450 at concentration of 1 uM significantly induces mRNAs encoding for BSEP, SHP, and IBABP in human cell cultures to 13-, 2-, and 20-fold, respectively. [1] WAY-362450 at concentration of 1 uM suppresses interleukin-6-induced CRP expression in human Hep3B hepatoma cells, and the inhibitory effect is attenuated when knockdown of FXR by short interfering RNA. |
In vivo |
WAY-362450 administrated intravenously or orally at does of 3 mg/kg in rats with a protracted half-life of 25 h, modest volume of distribution, and low clearance of 3.3 L/kg. WAY-362450 administered orally at dose of 10 mg/kg in normal C57bl/6 mice for a period of 7 days significantly lowers triglycerides to 62.0 +/- 6.4 mg/dL and total cholesterol to 78.1 +/- 5.0 mg/dL. WAY-362450 administered orally at dose of 1 and 3 mg/kg daily for 6 weeks in LDLR / mice, triglycerides is lowered by 19% and 39%, respectively, total cholesterol is lowered by 23% and 50%, respectively and lesion formation by 18% and 36%, respectively. [1] WAY-362450 intraperitoneally administrated at dose of 30 mg/kg daily for 4 days in wild type C57BL/6 mice attenuates lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver. [3] WAY-362450 orally administered at dose of 30 mg/kg/day for 4 weeks in adult male C57BL/6 mice reduces in ammatory cell in ltration and hepatic brosis, the reduction in in ammatory cell in ltration correlates with deceased serum levels of keratinocyte derived chemokine (mKC) and MCP 1 and decreased hepatic gene expression of MCP-1 and VCAM-1, and the reduction of hepatic brosis by WAY-362450 treatment corresponded to a reduction in hepatic gene expression of brosis markers. [3] WAY-362450 administrated orally at dose of 30mg/kg in LDLR / and apoE / mice blocks diet-induced hypertriglyceridemia and elevations of non-HDL cholesterol and produced a near complete inhibition of aortic lesion formation, WAY-362450 also induced small heterodimer partner (SHP) expression and repressed cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12 alpha-hydroxylase (CYP8B1) expression. [4] |
Molecular Weight (MW) |
438, 47 |
Picture ChemicalStructure Description |
WAY-362450 Chemical Structure |
Solubility (25C) |
DMSO 33 mg/mL, Water <1 mg/mL, Ethanol 2 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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