Gambogic Acid (Guttic Acid) ( EC50=0.78-1.64 uM) activates caspases. Gambogic Acid competitively suppresses Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1. The IC50s of Gambogic Acid for Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 are 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 uM, respectively.

Bfl-1:1.06μM, MCL1:0.79 μM, BCL2:1.21μM, BCL-XL:1.47μM, BCL-B:0.66μM, BCL-W:2.02μM

Gambogic Acid 是一种源自于Garcinia hanburyi 的笼型黄酮，通过抑制人类Bcl-2家族蛋白和激活caspases，在多种癌细胞中作为强效的凋亡诱导剂发挥作用。Gambogic Acid 同时以EC50 ≤ 100 nM 阻断Kir2.1 通道。[1] [2] [3] 此外，Gambogic Acid 在nM 浓度下显著抑制人脐静脉内皮细胞（HUVEC）的增殖、迁移、侵袭、管腔形成和微血管生长。[4]

Gambogic Acid 有效抑制肿瘤血管生成并通过小剂量化疗压制肿瘤生长，同时副作用低。[4]Gambogic Acid 具有多种功能效应，包括诱导凋亡、抑制增殖、防止癌症转移及肿瘤血管生成。[5]在动物肿瘤模型和临床试验中，Gambogic Acid 高效抑制肿瘤生长，且副作用小，对免疫和造血系统的毒性低。Gambogic Acid 能产生组织特异性蛋白酶体抑制和肿瘤特异性毒性。[6]LD50：小鼠45 mg/kg (i.p.)。[7]

The fluorescence polarization reactions are performed. For Kidetermination, duplicate 200 μL reactions are set up at eight different ATP concentrations from 200 μM (2-fold serial dilutions) in the presence of either DMSO or R406 at 125, 62.5, 31.25, 15.5, or 7.8 nM. At different time points, 20 μL of each reaction is removed and quenched to stop the reaction. For each concentration of R406, the rate of reaction at each concentration of ATP is determined and plotted against the ATP concentration to determine the apparent Km and Vmax (maximal rate). Finally the apparent Km (or apparent Km/Vmax) is plotted against the inhibitor concentration to determine the Ki. All data analysis is performed using Prism and Prism enzyme kinetics programs[1]