G007-LK

Catalog No.S7239 Batch:S723902

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Technical Data

Formula

C25H16ClN7O3S
Molecular Weight 529.96 CAS No. 1380672-07-0
Solubility (25°C)* In vitro DMSO 69 mg/mL (130.19 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description G007-LK is a potent and selective tankyrase inhibitor with IC50 of 46 nM and 25 nM for TNKS1/2, respectively.
Targets
TNKS2 [1]
(Cell-free assay)		 TNKS1 [1]
(Cell-free assay)
25 nM 46 nM
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[2]
  • Cell lines

    APC-mutant CRC cell lines COLO-320DM

  • Concentrations

    ~0.2 μM

  • Incubation Time

    7 to 13 days

  • Method

    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.
Animal Study:[2]
  • Animal Models

    Human APC –mutant CRC xenograft COLO-320DM

  • Dosages

    20 mg/kg

  • Administration

    i.p. twice daily

Customer Product Validation

, , Bone, 2018, 106:156-166

Selleck's G007-LK has been cited by 10 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.