XL335
3-(3,4-Difluorobenzoyl)-1,2,3,6-tetrahydro-1,1-dimethylazepino[4,5-b]indole-5-carboxylic acid 1-methylethyl ester
CAS: 629664-81-9
Molecular Formula: C25H24F2N2O3
XL335 - Names and Identifiers
XL335 - Physico-chemical Properties
| Molecular Formula | C25H24F2N2O3 |
| Molar Mass | 438.47 |
| Density | 1.275 |
| Boling Point | 617.3±55.0 °C(Predicted) |
| Solubility | DMSO : 25 mg/mL (57.02 mM; Need ultrasonic) |
| Appearance | powder |
| Color | white to beige |
| pKa | 16.49±0.60(Predicted) |
| Storage Condition | room temp |
| Use | Turofexorate isopropyl (FXR-450) is an effective, orally active, selective FXR agonist with an EC50 of 4 nM. |
| Target | FXR |
| In vitro study | WAY-362450 binds to the ligand binding domain (LBD) of human FXR. WAY-362450 is mainly found in hydrophobic bags, and only a few polar molecules come into contact with WAY-362450. In the promoter assay, WAY-362450 uses the reporter gene to promote transcription of human BSEP, human SHP, and mouse IBABP genes with EC50 of 17,230, and 33 nM, respectively. WAY-362450 significantly induced mRNAs encoding BSEP,SHP, and IBABP at 1 μm concentration, with effects in human cell culture of 13-,2-, and 20-fold. WAY-362450 inhibited IL-6-induced CRP expression in human Hep3B hepatoma cells at a concentration of 1 μm, and the inhibition was attenuated when FXR was interfered by short-chain RNA. |
| In vivo study | WAY-362450 administered intravenously or orally at a dose of 3 mg/kg has a durable half-life of 25 hours in rats with a moderate volume distribution volume, and a low clearance of 3.3 L/kg. Oral administration of WAY-362450 to normal C57bl/6 mice at a dose of 10 mg/kg for 7 days significantly reduced triglycerides to 62.0±6.4 mg/dL, total cholesterol was reduced to 78.1±5.0 mg/dL. WAY-362450 at a dose of 1 and 3 mg/kg/day to LDLR WAY-362450 at a dose of 30 mg/kg per day administered intraperitoneally to wild-type C57BL/6 mice for 4 days, attenuates lipopolysaccharide-induced serum amyloid P component and Serum Amyloid A3 mRNA levels in the liver. Oral administration of WAY-362450 at a dose of 30 mg/kg/day to adult male C57BL/6 mice reduces inflammatory cell infiltration and liver fibrosis, the reduction in inflammatory cell infiltration was associated with reduced serum levels of keratinocyte-derived chemokine (mKC) and MCP 1, as well as a MCP-1 and VCAM-1 reduction in hepatic gene expression, the reduction in liver fibrosis by WAY-362450 treatment is consistent with a reduction in liver gene expression of fibrosis markers. WAY-362450 LDLR at a dose of 30mg/kg |
XL335 - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.281 ml | 11.403 ml | 22.806 ml |
| 5 mM | 0.456 ml | 2.281 ml | 4.561 ml |
| 10 mM | 0.228 ml | 1.14 ml | 2.281 ml |
| 5 mM | 0.046 ml | 0.228 ml | 0.456 ml |
Last Update：2024-01-02 23:10:35
XL335 - Reference Information
| biological activity | Turofexorate Isopropyl (XL335, Fxr 450) is an effective and selective FXR agonist, EC50 is 4 nM, highly selective to act on other nuclear receptors, such as LXR, PPAR, ER, etc., Phase 1. |
| target | TargetValue FXR 4 nM(EC50) |
| Target | Value |
| FXR | 4 nM(EC50) |
| In vitro study | WAY-362450 and human FXR ligand binding domain (LBD) binding. WAY-362450 mainly exists in hydrophobic bags, and only a few polar molecules are in contact with WAY-362450. In promoter test, WAY-362450 used reporter gene to promote transcription of human BSEP, human SHP and mouse IBABP gene with EC50 of 17,230 and 33 nM respectively. WAY-362450 significantly induced the encoding of BSEP,SHP, and IBABP mRNAs at 1 μM concentration, and their effects in human cell cultures were 13-,2-, and 20-fold, respectively. WAY-362450 inhibits the expression of CRP induced by interleukin-6 in human Hep3B hepatoma cells at a concentration of 1 μM, and the inhibition is weakened when FXR is interfered by short-chain RNA. |
| in vivo study | WAY-362450 is administered intravenously or orally at a dose of 3 mg/kg, with a lasting half-life of 25 hours in rats, a moderate volume distribution volume, and a low clearance rate of 3.3 L/kg. WAY-362450 was orally administered to normal C57bl/6 mice at a dose of 10 mg/kg for 7 days, significantly reducing triglyceride to 62.0±6.4 mg/dL and total cholesterol to 78.1±5.0 mg/dL. WAY-362450 was administered intraperitoneally to wild-type C57BL/6 mice at doses of 1 and 3 mg/kg/day to LDLR WAY-362450 at doses of 30 mg/kg/day for 4 days, attenuating lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver. Oral administration of WAY-362450 to adult male C57BL/6 mice at a dose of 30 mg/kg/day reduces inflammatory cell infiltration and liver fibrosis. The decrease of inflammatory cell infiltration is related to the decrease of serum levels of keratinocyte-derived chemokine (mKC) and MCP 1, and the decrease of liver gene expression of MCP-1 and VCAM-1, the reduction of liver fibrosis by WAY-362450 treatment is consistent with the reduction of liver gene expression of fibrosis index. WAY-362450 to LDLR |
Last Update：2024-04-09 20:45:29
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Spot supply
Product Name: 3-(3,4-Difluorobenzoyl)-1,2,3,6-tetrahydro-1,1-dimethylazepino[4,5-b]indole-5-carboxylic acid 1-methylethyl ester Visit Supplier Webpage Request for quotationCAS: 629664-81-9
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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