G007-LK

製品コードS7239 バッチS723904

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H16ClN7O3S
分子量 529.96 CAS No. 1380672-07-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (188.69 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 G007-LK is a potent and selective tankyrase inhibitor with IC50 of 46 nM and 25 nM for TNKS1/2, respectively.
in vitro G007-LK reduces Wnt/β-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thereby promoting β-catenin destabilization. G007-LK completely blocks ligand-driven Wnt/β-catenin signaling in cell culture and display approximately 50% inhibition of APC mutation–driven signaling in most CRC cell lines. G007-LK (0.2 μM) reduces the number of COLO-320DM cells in mitosis from 24% to 12% and decreases HCT-15 cells in S-phase from 28% to 18%. G007-LK suppresses colony formation in CRC lines COLO-320DM and SW403. G007-LK suppresses organoids growth with IC50 of 80 nM. [2]
in vivo G007-LK exhibits antitumor efficacy in xenograft and genetically engineered CRC models. In the COLO-320DM model, G007-LK reduces tankyrases 1 and tankyrases 2 protein levels, stabilizes AXIN1 and AXIN2, and decreases β-catenin level. Wnt/β-catenin signaling is clearly inhibited in a dose-dependent manner in the efficacy study tumors as indicated by reduced expression of β-catenin–activated genes NKD1, APCDD1, and TNFRSF19 (TROY), as well as increased expression of β-catenin–repressed gene CLIC3. G007-LK treatment increases expression of KRT20 and TM4SF4 in COLO-320DM tumors. G007-LK (20 mg/kg twice daily) achieves 61% tumor growth inhibition. G007-LK reduces Wnt/β-catenin signaling and cell proliferation in normal intestine. [2]

プロトコル(参考用のみ)

キナーゼアッセイ TNKS1 and TNKS2 in vitro biochemical assays
G007-LK inhibitory activity at various doses (duplicates) is tested twice against TNKS1, TNSK2 Chemiluminescent Assay Kits, and the luminescence is measured on a GloMax Luminometer.
細胞アッセイ 細胞株 APC-mutant CRC cell lines COLO-320DM
濃度 ~0.2 μM
反応時間 7 to 13 days
実験の流れ For colony formation assays, cells are seeded at 500 cells/well in 2 mL of 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, changing medium and compound every third day. Colonies are stained by adding 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.
動物実験 動物モデル Human APC –mutant CRC xenograft COLO-320DM
投薬量 20 mg/kg
投与方法 i.p. twice daily

カスタマーフィードバック

, , Bone, 2018, 106:156-166

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase [ bioRxiv, 2024, 2024.02.02.578667] PubMed: 38352406
Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers [ Nat Commun, 2023, 14(1):110] PubMed: 36611031
Somatic tissue engineering in mouse models reveals an actionable role for WNT pathway alterations in prostate cancer metastasis. [ Cancer Discov, 2020, 6 pii: CD-19-1242] PubMed: 32376773
TDP-43 a Protein Central to Amyotrophic Lateral Sclerosis Is Destabilized by Tankyrase-1/2 [ J Cell Sci, 2020, 14;jcs245811] PubMed: 32409565
Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status. [ J Clin Med, 2020, 30;9(4)] PubMed: 32235451
Tankyrase promotes primary precursor miRNA processing to precursor miRNA. [ Biochem Biophys Res Commun, 2020, 522(4):945-951] PubMed: 31806370
[ PLoS ONE, 2019, ] PubMed: 31891587
Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization [ Mol Cell, 2018, 71(5):703-717.e9] PubMed: 30100264
MERIT40-dependent recruitment of tankyrase to damaged DNA and its implication for cell sensitivity to DNA-damaging anticancer drugs. [ Oncotarget, 2018, 9(88):35844-35855] PubMed: 30533199
Pharmacological inhibition of tankyrase induces bone loss in mice by increasing osteoclastogenesis. [Fujita S, et al. Bone, 2017, S8756-3282(17)30383-6] PubMed: 29055830

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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