Turofexorate Isopropyl (XL335)

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.

4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1], 4 nM [1]

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]

WAY-362450 Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO