G007-LK是一种有效的、选择性的TNKS1（IC50=46nM）和TNKS2（IC50=25nM）抑制剂。
Cas No.:1380672-07-0
Sample solution is provided at 25 µL, 10mM.
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G007-LK is a potent and selective inhibitor of TNKS1 (IC50=46nM) and TNKS2 (IC50=25nM)[1-2]. G007-LK reduces Wnt/β-catenin signaling by inhibiting tankyrase, which prevents AXIN degradation and promotes β-catenin destabilization. G007-LK is used in research related to colorectal cancer, hepatocellular carcinoma, and small cell lung cancer[3-4].
In vitro, G007-LK (50-1000nM) was used to treat patient-derived glioma stem cells (GSCs) for 14 days. G007-LK significantly inhibited the proliferation and sphere formation of GSCs, reduced the expression of downstream target genes of the WNT/β-catenin and YAP/TAZ signaling pathways, and stabilized AXIN1, AMOT, and AMOTL2 proteins[5]. G007-LK (2.5-20μM) was also used to treat human hepatocellular carcinoma (HCC) cell lines for 10-14 days. G007-LK significantly inhibited the colony-forming ability of HCC cells, downregulated YAP protein levels and its downstream target gene expression, and upregulated AMOTL1 and AMOTL2 proteins[6].
In vivo, G007-LK (14mg/kg/day) was administered via diet to db/db diabetic mice, starting at 6 weeks of age for 15 weeks. G007-LK significantly reduced body weight, abdominal fat content, hepatic steatosis, and serum cholesterol levels, while increasing white adipose tissue browning, serum adiponectin levels, mitochondrial mass, and fatty acid oxidative metabolism in skeletal muscle[7]. G007-LK (0.015% wt/wt mixed into diet) was also fed to high-fat diet-fed wild-type male mice for 6 months. G007-LK significantly improved glucose tolerance, enhanced insulin sensitivity, and rapidly increased plasma adiponectin levels[8].
References:
[1] Voronkov A, Holsworth DD, Waaler J, et al. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor. J Med Chem. 2013 Apr 11;56(7):3012-23.
[2] Norum JH, Skarpen E, Brech A, et al. The tankyrase inhibitor G007-LK inhibits small intestine LGR5+ stem cell proliferation without altering tissue morphology. Biol Res. 2018 Jan 9;51(1):3.
[3] Jia J, Qiao Y, Pilo MG, et al. Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade. PLoS One. 2017 Sep 6;12(9):e0184068.
[4] Thorvaldsen TE, Pedersen NM, Wenzel EM, et al. Structure, Dynamics, and Functionality of Tankyrase Inhibitor-Induced Degradasomes. Mol Cancer Res. 2015 Nov;13(11):1487-501.
[5] Kierulf-Vieira KS, Sandberg CJ, Waaler J, et al. A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation. Cancers (Basel). 2020 Jun 19;12(6):1630.
[6] Jia J, Qiao Y, Pilo MG, et al. Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade. PLoS One. 2017 Sep 6;12(9):e0184068.
[7] Wang H, Kuusela S, Rinnankoski-Tuikka R, et al. Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice. Int J Obes (Lond). 2020 Aug;44(8):1691-1702.
[8] Zhong L, Ding Y, Bandyopadhyay G, et al. The PARsylation activity of tankyrase in adipose tissue modulates systemic glucose metabolism in mice. Diabetologia. 2016 Mar;59(3):582-91.
G007-LK是一种有效的、选择性的TNKS1（IC50=46nM）和TNKS2（IC50=25nM）抑制剂[1-2]。G007-LK可通过抑制tankyrase来减少Wnt/β-catenin信号传导，防止AXIN降解，促进β-catenin去稳定化。G007-LK可用于结直肠癌、肝细胞癌、小细胞肺癌等相关研究[3-4]。
在体外，G007-LK（50-1000nM）处理人源胶质瘤干细胞（GSCs）14天，G007-LK显著抑制GSCs的增殖和肿瘤球形成，并降低WNT/β-catenin和YAP/TAZ信号通路下游靶基因（如AXIN2、CTGF）的表达，同时稳定AXIN1、AMOT和AMOTL2蛋白[5]。G007-LK（2.5-20μM）处理人源肝细胞癌（HCC）细胞系10-14天，G007-LK显著抑制HCC细胞的集落形成能力，并下调YAP蛋白水平及其下游靶基因（如CTGF、CYR61）的表达，同时上调AMOTL1和AMOTL2蛋白[6]。
在体内，G007-LK（14mg/kg/day）饲喂处理db/db糖尿病小鼠（从6周龄开始，持续15周），G007-LK显著降低小鼠体重、腹部脂肪含量、肝脏脂肪变性和血清胆固醇水平，并增加白色脂肪组织（WAT）褐变、血清脂联素水平以及骨骼肌的线粒体质量和脂肪酸氧化代谢[7]。G007-LK（混入饲料， 0.015%wt/wt）饲喂处理高脂饮食（HFD）喂养的野生型雄性小鼠（持续6个月），G007-LK显著改善葡萄糖耐量、增强胰岛素敏感性，并迅速提高血浆脂联素水平[8]。
| Cell experiment [1]: | |
Cell lines | Patient-derived glioma stem cell (GSC) cultures (T0965, T1008, T1023, T2609) and adult human neural stem cell (ahNSC) cultures (H1515, H1517) |
Preparation Method | GSCs were cultured as spheres in serum-free, growth factor-enriched DMEM/F12 medium. Cells were treated with G007-LK (50-1000nM) for 14 days under sphere-forming conditions. |
Reaction Conditions | 50-1000nM; 14 day. |
Applications | G007-LK treatment significantly and dose-dependently reduced the in vitro proliferation and sphere formation capacity of all four primary GSC cultures. G007-LK treatment stabilized AXIN1, TNKS1/2, AMOT, and AMOTL2 proteins, and reduced the expression of WNT/β-catenin (e.g., AXIN2, DKK1) and YAP/TAZ (e.g., CTGF, CYR61) downstream target genes. The proliferation of normal ahNSC cultures was unaffected by 100nM G007-LK treatment. |
| Animal experiment [2]: | |
Animal models | Diabetic male C57BLKS/J db/db mice |
Preparation Method | Mice were individually housed and fed from 6 weeks of age for 15 weeks with normal chow or chow supplemented with the selective TNKS inhibitor G007-LK. The average daily dose for db/db mice was 14mg/kg/day, incorporated into the diet. |
Dosage form | 14mg/kg/day; mixed into the diet; for 15 weeks. |
Applications | Long-term G007-LK treatment in db/db mice significantly reduced body weight gain, abdominal adiposity, and hepatic steatosis, and lowered serum levels of total, LDL, and HDL cholesterol. G007-LK treatment upregulated adiponectin levels in white adipose tissue (WAT) and serum, and suppressed proteins associated with lipolysis (ATGL and p-HSL) in WAT. G007-LK induced beiging of WAT, evidenced by increased UCP-1 protein. In skeletal muscle, G007-LK increased mitochondrial mass and fatty acid oxidative metabolism. Importantly, the treatment ameliorated lipid disorder without causing intestinal toxicity or affecting liver PGC-1α expression, gluconeogenesis, or lipid metabolism. |
References: | |
| Cas No. | 1380672-07-0 | SDF | |
| 别名 | Tankyrase 1/2 Inhibitor VI | ||
| 化学名 | (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 | ||
| Canonical SMILES | CS(C1=CN=C(C2=NN=C(N2C3=CC=CC=C3Cl)/C([H])=C([H])/C(O4)=NN=C4C5=CC=C(C#N)C=C5)C=C1)(=O)=O | ||
| 分子式 | C25H16ClN7O3S | 分子量 | 529.96 |
| 溶解度 | ≥ 26.5mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8869 mL | 9.4347 mL | 18.8693 mL |
| 5 mM | 377.4 μL | 1.8869 mL | 3.7739 mL |
| 10 mM | 188.7 μL | 943.5 μL | 1.8869 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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