关附甲素

概述生物活性靶点体外研究体内研究关附甲素试剂级价格

关附甲素

CAS号:1394-48-5
英文名:Guan-fu base A
中文名:关附甲素
CBNumber:CB91341165
分子式:C24H31NO6
分子量:429.51
MOL File:1394-48-5.mol

关附甲素化学性质

沸点 :541.5±50.0 °C(Predicted)
密度 :1.43±0.1 g/cm3(Predicted)
储存条件 :4°C, away from moisture and light
酸度系数(pKa) :12.97±0.70(Predicted)
形态 :Solid
颜色 :White to off-white

关附甲素性质、用途与生产工艺

概述关附甲素是中药毛茛科黄花乌头中的主要活性物质之一。临床前药理研究表明：盐酸关附甲素可对抗高钙、结扎冠状动脉及乌头碱诱发的室性心动过速和心室颤动，并可对抗乙酰胆碱诱发的心房扑动和心房颤动；可浓度依赖性降低对心肌快反应动作电位的Vmax。
生物活性 Guanfu base A 是一种从 Aconitum coreanum 中分离的抗心律失常的生物碱，是一种有效的非竞争性 CYP2D6 抑制剂，对人肝微粒体 (HLM) 的 Ki 为 1.20 μM，对人重组体 (rCYP2D6) 的 Ki 为 0.37 μM。Guanfu base A 也是 CYP2D 的有效竞争抑制剂，对猴子和狗的微粒体的 Ki 分别为 0.38 μM，2.4 μM。Guanfu base A 还能抑制 HERG 通道电流。
靶点

CYP2D6; HERG channel
体外研究

Guanfu base A has no inhibitory activity on mouse or rat CYP2Ds. Guanfu base A does not exhibit any inhibition activity on human recombinant CYP1A2, 2A6, 2C8, 2C19, 3A4, or 3A5, but shows slight inhibition of 2B6 and 2E1.
Guanfu base A is a potent inhibitor of CYP2D6, with an IC ₅₀ recorded at ~0.46 μM in HLM (Dextromethorphan 5 μM) and 0.12 μM in rCYP2D6 (Bufuralol 5 μM).
The effects of Guanfu base A is investigated in human embryonic kidney 293 (HEK293) cells transiently transfected with HERG complementary DNA using a whole-cell patch clamp technique. Guanfu base A inhibits HERG channel current in concentration-, voltage-, and time-dependent manners with an IC ₅₀ of 1.64 mM. Guanfu base A shifts the activation curve in a negative direction and accelerated channel inactivation but shows no effect on the inactivation curve.
体内研究

Beagle dogs treated intravenously with Dextromethorphan (2 mg/mL) after pretreatment with Guanfu base A injection shows reduced CYP2D metabolic activity, with the C _max of dextrorphan being one-third that of the saline-treated group and area under the plasma concentration-time curve half that of the saline-treated group.
化学性质白色结晶，可溶于甲醇、乙醇、DMSO等有机溶剂，来源于毛茛科植物黄花乌头的块根（关白附）。
用途关附甲素具有抗心律失常的作用。