1380672-07-0
1380672-07-0 structure
- Name: G007-LK
- Chemical Name: (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
- CAS Number: 1380672-07-0
- Molecular Formula: C25H16ClN7O3S
- Molecular Weight: 529.95800
- Catalog: Signaling Pathways Cell Cycle/DNA Damage PARP
- Create Date: 2017-05-04 11:06:10
- Modify Date: 2024-01-02 12:21:06
-
G007-LK is a potent and selective inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively.
| Name | (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 |
|---|---|
| Synonyms | G007-LK |
| Description | G007-LK is a potent and selective inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
TNKS2:25 nM (IC50) TNKS1:46 nM (IC50) |
| In Vitro | G007-LK is a potent inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively, and a cellular IC50 of 50 nM. G007-LK shows no inhibition of PARP1 at doses up to 20 μM, and has a high CYP3A4 inhibition IC50 value (>25 μM)[1]. 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[3]. |
| In Vivo | G007-LK displays great pharmacokinetic profile in ICR mice[1]. 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[2]. |
| Cell Assay | For cell proliferation or apoptosis assays, SNU-449 and HLE cells are grown in a 5% CO2 atmosphere, at 37°C, in RPMI Medium supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin. HCC cells are treated with 0.1% DMSO, or 2.5 μM, 5 μM, 10 μM, 20μM XAV-939 or G007-LK, either alone or in combination with the MEK inhibitor U0126 (25 μM) or the AKT inhibitor MK-2206 (5 μM). Cell proliferation is analyzed using the BrdU Cell Proliferation Assay Kit, while apoptosis is assessed with the Cell Death Detection Elisa Plus Kit[3]. |
| Animal Admin | Drug treatment experiments are performed with wild type (wt), single or double transgenic Lgr5-EGFP-Ires-CreERT2;R26R-Confetti mice, unless indicated otherwise. G007-LK is administered orally either by gavage (10 or 50 mg/kg body mass once daily, vehicle: 15% dimethylsulfoxide [DMSO], 17.5% Cremophor EL, 8.75% Miglyol 810 N, 8.75% ethanol in phosphate buffered saline [PBS]) or in G007-LK enriched chow (100 or 1000 mg G007-LK/kg chow ad libitum, corresponding to a daily G007-LK dose of approximately 20 or 200 mg/kg body mass, respectively, for a mouse with a body mass of 25 g and consumption of approximately 5 g enriched diet/day). G007-LK treatments are initiated at the age of 5 weeks and 5 days for oral gavage treatment or 6 weeks for enriched chow administration and continued for 9 or 21 days, respectively[2]. |
| References |
| Molecular Formula | C25H16ClN7O3S |
|---|---|
| Molecular Weight | 529.95800 |
| Exact Mass | 529.07200 |
| PSA | 148.83000 |
| LogP | 5.55908 |
| Storage condition | 2-8°C |