中文同义词:
4-[5-[(1E)-2-[4-(2-氯苯基)-5-[5-(甲基磺酰基)-2-吡啶基]-4H-1,2,4-三唑-3-基]乙烯基]-1,3,4-恶二唑-2-基]苯甲腈;TANKYRASE抑制剂(G007-LK);G007-LK游离态
英文同义词:
G007-LK;(E)-4-(5-(2-(4-(2-chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)vinyl)-1,3,4-oxadiazol-2-yl)benzonitrile;4-[5-[(1E)-2-[4-(2-Chlorophenyl)-5-[5-(methylsulfonyl)-2-pyridinyl]-4H-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]benzonitrile;Benzonitrile, 4-[5-[(1E)-2-[4-(2-chlorophenyl)-5-[5-(methylsulfonyl)-2-pyridinyl]-4H-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]-;G007-LK;G007 LK;G007LK;CS-1659;Tankyrase 1/2 Inhibitor VI, G007-LK - Calbiochem;G007 LK;G007LK
沸点
817.3±75.0 °C(Predicted)
密度
1.47±0.1 g/cm3(Predicted)
酸度系数(pKa)
-1.68±0.10(Predicted)
生物活性
G007-LK是一种有效的选择性tankyrase抑制剂，对TNKS1/2的IC50分别为46 nM 和 25 nM。
靶点
Target Value
TNKS2
(Cell-free assay) 25 nM
TNKS1
(Cell-free assay) 46 nM
TNKS2
(Cell-free assay)
25 nM
TNKS1
(Cell-free assay)
46 nM
体外研究
G007-LK is a potent inhibitor of TNKS1 and TNKS2, with IC 50 s of 46 nM and 25 nM, respectively, and a cellular IC 50 of 50 nM. G007-LK shows no inhibition of PARP1 at doses up to 20 μM, and has a high CYP3A4 inhibition IC 50 value (>25 μM). G007-LK (0-20 μM) dose-dependently inhibits hepatocellular carcinoma (HCC) cell growth. G007-LK also downregulates the levels of YAP by upregulating AMOTL1 and AMOTL2 in HCC cell lines. In addition, G007-LK (0-20 μM) synergizes with MEK and AKT inhibitors to suppress HCC cell proliferation.
体内研究
G007-LK displays great pharmacokinetic profile in ICR mice. G007-LK (100 mg/kg chow, p.o.) significantly reduces lineage tracing from LGR5 + intestinal stem cells in mice. G007-LK (100 mg/kg chow, p.o.) specifically targets LGR5 + WNT-dependent intestinal stem cells in Lgr5-EGFP-CreERT2;R26R-tdTomato mice. G007-LK (10, 50 mg/kg, p.o.) also suppressses canonical WNT signalling. Furthermore, G007-LK (100, 1000 mg/kg chow, p.o) shows no effect on the alteration of duodenal morphology.
