Name | G007-LK |
Description | G007-LK is a selective inhibitor of TNKS1 and TNKS2, with IC50s of 46 nM and 25 nM, respectively. |
Cell Research | 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. |
Kinase Assay | TNKS1 and TNKS2 in vitro biochemical assays: G007-LK inhibitory activity at various doses (duplicates) is tested twice by TNKS1, TNSK2 Chemiluminescent Assay Kits, and the luminescence is measured. |
Animal Research | 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 |
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。 |
Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
Solubility Information | Ethanol : < 1 mg/mL (insoluble or slightly soluble) H2O : < 1 mg/mL (insoluble or slightly soluble) DMSO : 93 mg/mL (175.5 mM)
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Keywords | G007LK | Inhibitor | poly ADP ribose polymerase | G-007-LK | G007 LK | PARP | inhibit | G007-LK |
Inhibitors Related | Urea | Bisdemethoxycurcumin | VPC-70063 | Niraparib | Nefopam hydrochloride | XAV-939 | Olaparib | 3-Aminobenzamide | Benzamide | OUL35 | CHIR-99021 | Wnt pathway activator 1 |
Related Compound Libraries | Neuroprotective Compound Library | Inhibitor Library | Anti-Breast Cancer Compound Library | Bioactive Compound Library | Bioactive Compounds Library Max | Anti-Aging Compound Library | Epigenetics Compound Library | NO PAINS Compound Library | Neuronal Differentiation Compound Library | Wnt/Hedgehog/Notch Compound Library |