G007-LK effectively inhibits TNKS1 and TNKS2, with IC50 values of 46 nM and 25 nM, respectively, and demonstrates a cellular IC50 of 50 nM. It does not inhibit PARP1 at concentrations up to 20 μM and possesses a high IC50 value for CYP3A4 inhibition (>25 μM)[1]. G007-LK (0-20 μM) inhibits the growth of hepatocellular carcinoma (HCC) cells in a dose-dependent manner. It reduces YAP levels by increasing AMOTL1 and AMOTL2 in HCC cell lines. Moreover, G007-LK (0-20 μM) works in synergy with MEK and AKT inhibitors to curb HCC cell proliferation[3].
体内研究
G007-LK exhibits an excellent pharmacokinetic profile in ICR mice[1].
G007-LK (100 mg/kg chow, pO.) significantly diminishes lineage tracing from LGR5+ intestinal stem cells in mice, specifically targeting LGR5+ WNT-dependent intestinal stem cells in Lgr5-EGFP-CreERT2;R26R-tdTomato mice. G007-LK (10, 50 mg/kg, pO.) also reduces canonical WNT signaling. Additionally, G007-LK (100 mg/kg chow, pO.) does not affect duodenal morphology[2].
体外研究
G007-LK effectively inhibits TNKS1 and TNKS2, with IC50 values of 46 nM and 25 nM, respectively, and demonstrates a cellular IC50 of 50 nM. It does not inhibit PARP1 at concentrations up to 20 μM and possesses a high IC50 value for CYP3A4 inhibition (>25 μM)[1].
G007-LK (0-20 μM) inhibits the growth of hepatocellular carcinoma (HCC) cells in a dose-dependent manner. It reduces YAP levels by increasing AMOTL1 and AMOTL2 in HCC cell lines. Moreover, G007-LK (0-20 μM) works in synergy with MEK and AKT inhibitors to curb HCC cell proliferation[3].
G007-LK 细胞实验
Cell Line
Concentration
Treated Time
Description
References
H58 cells
0, 0.1, 0.5, 1, 2, 4 μM
96 h
To evaluate the cytotoxicity of G007-LK on H58 cells, the results showed that H58 cells were not sensitive to G007-LK, as IC50 was not reached even at a concentration of 4 μM.
G007-LK induced AMPK activation without altering LKB1/AMPK levels.
Nat Commun. 2019 Sep 25;10(1):4363.
U2OS cells
5 μM
12 h
G007-LK induced AMPK activation.
Nat Commun. 2019 Sep 25;10(1):4363.
COLO 320DM
1 µM
24 h
Inhibition of WNT/β-catenin signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth
iScience. 2021 Jul 1;24(7):102807.
UO-31
1 µM
24 h
Inhibition of YAP signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth
iScience. 2021 Jul 1;24(7):102807.
OVCAR-4
1 µM
24 h
Inhibition of WNT/β-catenin and YAP signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth
iScience. 2021 Jul 1;24(7):102807.
ABC-1
1 µM
24 h
Inhibition of PI3K/AKT signaling, reduction of MYC and CCND1 expression, leading to impaired cell growth
iScience. 2021 Jul 1;24(7):102807.
shApc organoids
1μM
3 days
To evaluate the effect of G007-LK on shApc organoids, results showed that G007-LK-treated shApc organoids underwent rapid cell cycle arrest, and induced Krt20 expression while reducing Lgr5 expression.
Cancer Discov. 2019 Oct;9(10):1358-1371.
ApcMin organoids
1μM
3 days
To evaluate the effect of G007-LK on ApcMin organoids, results showed that G007-LK-treated ApcMin organoids maintained a proliferative phenotype, with no significant changes in Krt20 and Lgr5 expression observed.
Cancer Discov. 2019 Oct;9(10):1358-1371.
G007-LK 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SCID mice
ALK1510-c4 cells xenograft model
Oral
10 mg/kg or 50 mg/kg
Once daily for 14 days
To evaluate the inhibitory effect of AZ6102 in combination with alectinib on tumor growth. Results showed that the combination significantly suppressed tumor growth.
NPJ Precis Oncol. 2024 Nov 17;8(1):264.
Mice
Diabetic mouse model
Intraperitoneal injection
30 mg/kg
Once daily for 30 days
G007-LK significantly reduced blood glucose levels and improved glycemic control in diabetic mice.
Nat Commun. 2019 Sep 25;10(1):4363.
Mice
Lgr5 -EGFP -Ires-CreERT2;R26R -Confetti mice
Oral
10 or 50 mg/kg
Once daily, for 9 days
To assess the effect of G007-LK on duodenal stem cell homeostasis and intestinal epithelium integrity. Results showed that G007-LK inhibited WNT signaling in LGR5+ stem cells and reduced the number and distribution of cells traced from duodenal LGR5+ stem cells, but the morphology of the duodenum remained unchanged, and the mice did not show weight loss or other visible morphological changes.
Biol Res. 2018 Jan 9;51(1):3
BALB/c nude mice
SW480 and RKO CDX mouse models
Intraperitoneal injection
20 mg/kg
Once daily for 16 days
G007-LK failed to restrain tumor growth in SW480 CDX model
Acta Pharm Sin B. 2024 Jan;14(1):207-222
Mice
TG-shApc mouse model
Intraperitoneal injection
30mg/kg
Once daily for one week
To evaluate the effect of G007-LK on tumors in the TG-shApc mouse model, results showed that G007-LK-treated tumors had reduced BrdU incorporation, loss of Lgr5 expression, and induction of both Krt20 and ALPi.
Cancer Discov. 2019 Oct;9(10):1358-1371.
Mice
EGFR mutant PDX model
Intraperitoneal
20 mg/kg
5 days a week
Combination of G007-LK with osimertinib did not achieve greater tumor growth inhibition than osimertinib monotherapy alone
Cancer Discov. 2021 Dec 1;11(12):3028-3047
BALB/c nude mice
SW480 and RKO CDX mouse models
Intraperitoneal injection
20 mg/kg
Once daily for 16 days
G007-LK failed to inhibit tumor growth in SW480 and RKO CDX mouse models
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