ACT 058362; PALOSURAN,

生物活性靶点体外研究体内研究 ACT 058362; PALOSURAN, 试剂级价格

CAS号:540769-28-6
英文名:Urea, N-[2-[4-hydroxy-4-(phenylMethyl)-1-piperidinyl]ethyl]-N'-(2-Methyl-4-quinolinyl)-
中文名:ACT 058362; PALOSURAN,
CBNumber:CB42628509
分子式:C25H30N4O2
分子量:418.53
MOL File:540769-28-6.mol

ACT 058362; PALOSURAN,化学性质

沸点 :612.9±55.0 °C(Predicted)
密度 :1.235±0.06 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :DMF: 10 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml; Ethanol: 0.5 mg/ml
形态 :A crystalline solid
酸度系数(pKa) :12.95±0.43(Predicted)
颜色 :White to pink

ACT 058362; PALOSURAN,性质、用途与生产工艺

生物活性 Palosuran (ACT-058362) 是一种有效，选择性和具有口服活性的 urotensin II receptor 受体拮抗剂，对于表达人重组受体的 CHO 细胞膜的 IC50 值为 3.6 nM。Palosuran 可改善糖尿病大鼠的胰腺和肾脏功能。
靶点

IC50: 3.6 nM (human urotensin II receptor)
体外研究

Palosuran (8 h) inhibits ¹²⁵ I-U-II binding to human UT receptor, with IC ₅₀ s of 46.2 nM on TE 671 cells and 86 nM on recombinant CHO cells.
Palosuran inhibits Ca ²⁺ mobilization in response to human U-II in CHO cells expressing human and rat UT receptor with IC ₅₀ s of 17 and >10000 nM, respectively.
Palosuran (0.12-10000 nM; 20 min) inhibits human U-II induced MAPK phosphorylation in a dose-dependent manner in recombinant CHO cells, with an IC ₅₀ of 150 nM.

体内研究

ACT-058362 (10 mg/kg/h; i.v.) fully prevents the decrease in renal blood flow after ischemia in rats without decreasing blood pressure.
Palosuran (300 mg/kg/d; p.o. for 16 weeks) improves the survival, increases insulin, and slows the increase in glycemia, glycosylated hemoglobin, and serum lipids in streptozotocin-induced diabetic rats.

Animal Model:	Male Wistar rats with renal ischemia and reperfusion
Dosage:	20 mg/kg/h for 135 min
Administration:	I.v. (continuous infusion) for 135 min
Result:	Restored renal blood flow to baseline values at 30 min after reperfusion and by 60 min increased renal blood flow by 12% above baseline values. Did not significantly alter mean arterial blood pressure (MAP) and heart rate (HR).