Raloxifene 6-glucuronide is a metabolite of the selective estrogen receptor modulator raloxifene . It is formed from raloxifene via the UDP-glucuronosyltransferase (UGT) isoforms UGT1A1 and UGT1A8. It binds to the estrogen receptor with an IC value of 290 nM. Unlike raloxifene, raloxifene 6-glucuronide does not inhibit the voltage-gated potassium channel K4.3.
Raloxifene 6-Glucuronide is a primary metabolite of Raloxifene. Raloxifene 6-glucuronide is mediated mostly by UGT1A1 and UGT1A8. Raloxifene 6-glucuronide binds to estrogen receptor with an IC50 of 290 μM. Raloxifene is a selective and nonsteroidal estrogen receptor modulator. Raloxifene activates TGFβ3 promoter as a full agonist at nanomolar concentrations, and inhibits the estrogen response element-containing vitellogenin promoter expression.
体外研究
Expressed UGT1A8 catalyzes Raloxifene 6-glucuronide with an apparent Km of 7.9 μM and a Vmax of 0.61 nmol/min/mg of protein. Based on rates of Raloxifene glucuronidation and known extrahepatic expression, UGT1A8 and 1A10 appear to be primary contributors to Raloxifene glucuronidation in human jejunum microsomes. For human liver microsomes, the variability of Raloxifene 6-glucuronide formation is 3-fold. Correlation analyses reveals that UGT1A1 is responsible for Raloxifene 6-glucuronide but not Raloxifene 4'-glucuronide in liver. Treatment of expressed UGTs with alamethicin results in minor increases in enzyme activity, whereas in human intestinal microsomes, maximal increases of 8-fold for the Raloxifene 6-glucuronide are observed. Intrinsic clearance values in intestinal microsomes are 17 μl/min/mg for the Raloxifene 6-glucuronide.
分子式
C34H35NO10S
分子量
649.71
CAS号
174264-50-7
中文名称
雷洛昔芬d4-6葡糖苷酸
运输条件
Room temperature in continental US; may vary elsewhere.