| Description | G007-LK is a selective inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively. |
| In vitro | G007-LK在异种移植和基因工程CRC模型中显示出抗肿瘤效力.在COLO-320DM模型中,G007-LK降低了tankyrases 1和tankyrases 2蛋白水平,稳定了AXIN1和AXIN2,并降低了β-catenin水平.G007-LK治疗增加COLO-320DM肿瘤中KRT20和TM4SF4的表达. G007-LK（20 mg/kg每日两次）达到61％的肿瘤生长抑制.G007-LK降低正常肠道中的Wnt/β-连环蛋白信号传导和细胞增殖. |
| In vivo | G007-LK通过防止多聚（ADP-核糖基）依赖性的AXIN降解来降低Wnt /β-连环蛋白信号传导,由此促进β-连环蛋白去稳定化。G007-LK在细胞培养中完全阻断配体驱动的Wnt/β-连环蛋白信号传导,并在大多数CRC细胞系中显示对约50％APC突变驱动的信号传导的抑制。 G007-LK（0.2 μM）将有丝分裂中的COLO-320DM细胞数量从24％降低至12％,并将S期中的HCT-15细胞从28％降低至18％。G007-LK抑制CRC系列COLO-320DM和SW403中的集落形成。 G007-LK抑制器官生长,IC50为80 nM。 |
| Cell experiments | Cell lines: APC-mutant CRC cell lines COLO-320DM. Concentrations: ~0.2 μM. Method: For colony formation assays,cells are seeded at 500 cells/well in 2 mL medium.Cell line in triplicate wells is treated with either 0.06% DMSO or compound in 0.06% DMSO and incubated for up to 17 days or until colonies became sufficiently large to quantify.Colonies are stained with 200 μL of 12 mM 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to each well for 1 h,and colony numbers are quantitated with a GelCount scanner at 1200 dpi resolution. |
| Animal experiments | Animal Models: Human APC –mutant CRC xenograft COLO-320DM. Formulation: 15% DMSO,17.5% Cremophor EL,8.75% ethanol,8.75% Miglyol 810N,50% PBS. Dosages: 20 mg/kg. Administration: intraperitoneal injection twice daily |
| Target activity | TNKS1:46 nM, TNKS2:25 nM |
| molecular weight | 529.96 |
| Molecular formula | C25H16ClN7O3S |
| CAS | 1380672-07-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | Ethanol: < 1 mg/mL (insoluble or slightly soluble) H2O: < 1 mg/mL (insoluble or slightly soluble) DMSO: 93 mg/mL (175.5 mM) |
| References | 1. Voronkov A, et al. J Med Chem, 2013, 56(7), 32012-3023. 2. Lau T, et al. Cancer Res, 2013, 73(10), 3132-3144. |