G007-LK

SKU: orb1300415

Description

G007-LK is a potent and selective dual inhibitor of tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2), exhibiting IC50 values of 46 nM and 25 nM, respectively. This small molecule is a valuable chemical probe for studying Wnt/β-catenin signaling in cancer research and has been utilized in both cellular and in vivo models to investigate tankyrase function.

Research Area

Epigenetics & Chromatin, Molecular Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1380672-07-0
• MW: 529.96
• Purity: 98.62% (May vary between batches)
• Formula: C₂₅H₁₆ClN₇O₃S
• SMILES: CS(=O)(=O)c1ccc(nc1)-c1nnc(\C=C\c2nnc(o2)-c2ccc(cc2)C#N)n1-c1ccccc1Cl
• Target: PARP,Wnt/beta-catenin
• Solubility: 10% DMSO+90% Corn Oil:3.3 mg/mL (6.23 mM);DMSO:93 mg/mL (175.48 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  TNKS2:25 nM|TNKS1:46 nM
• In Vivo:
  G007-LK inhibits Wnt/β-catenin signaling by preventing poly(ADP-ribosyl)ation-dependent AXIN degradation, thus promoting β-catenin destabilization. In cell culture, it completely blocks ligand-driven Wnt/β-catenin signaling and demonstrates inhibition of approximately 50% in APC mutation-driven signaling across most CRC cell lines. G007-LK reduces mitotic COLO-320DM cells from 24% to 12% and S-phase HCT-15 cells from 28% to 18% at a concentration of 0.2 μM. It also inhibits colony formation in CRC cell lines COLO-320DM and SW403. Furthermore, G007-LK suppresses organ growth with an IC50 of 80 nM.
• In Vitro:
  G007-LK demonstrated anti-tumor efficacy in xenograft and genetically engineered CRC models. In the COLO-320DM model, it reduced levels of tankyrases 1 and 2, stabilized AXIN1 and AXIN2, and decreased β-catenin levels. G007-LK treatment increased the expression of KRT20 and TM4SF4 in COLO-320DM tumors. Administered at 20 mg/kg twice daily, G007-LK achieved a 61% inhibition of tumor growth. Additionally, it reduced Wnt/β-catenin signaling and cell proliferation in normal intestinal tissue.
• 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.
• 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

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, G007 LK, G007LK, G-007-LK, G007-LK, inhibit, PARP, bcatenin, beta-catenin, betacatenin, Wnt, Wnt/b-catenin, Wnt/betacatenin, Wnt/β-catenin, poly ADP ribose polymerase, TNKS1, TNKS2, βcatenin

Compound Identifiers

PubChem CID

67960134