KYA1797K

SKU: orb1300392

Description

KYA1797K is a potent and selective small molecule inhibitor of the Wnt/β-catenin signaling pathway, demonstrating an IC50 of 0.75 μM in a TOPflash reporter assay. This inhibitor is a valuable chemical probe for investigating Wnt-driven processes in cancer and stem cell biology, applicable in both cellular and in vivo research models.

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1956356-56-1
• MW: 442.51
• Purity: 99.33% (May vary between batches)
• Formula: C₁₇H₁₁N₂O₆S₂·K
• SMILES: [K+].[O-]C(=O)CCN1C(=S)S\C(=C/c2ccc(o2)-c2ccc(cc2)[N+]([O-])=O)C1=O
• Target: Wnt/beta-catenin
• Solubility: DMSO:6 mg/mL (13.56 mM)

Bioactivity

• Target IC50:
  Wnt/β-catenin:0.75 μM
• In Vivo:
  KYA1797K administration by intraperitoneally injection(i.p.) (25 mg/kg) reduces both weight and volume of the tumor by 70% in mice carrying xenografted tumors from the D-MT cell line that harbors both APC and KRAS mutations. KYA1797K treatment significantly reduces levels of β-catenin and Ras proteins as well as Wnt/β-catenin and Ras signaling target. No change in the weight and no abnormalities in liver tissues of mice treated with KYA1797K. KYA1797K significantly reduces the subcellular localization of β-catenin in the nuclei and pan-Ras on the membrane of tumor cells. Thus, KYA1797K has anti-tumor effect.
• In Vitro:
  KYA1797K significantly decreases reporter activities for the Wnt/β-catenin and MAPK/ERK pathways but does not affect the reporter activities of other cancer-related pathways, such as the Notch and TGFβ pathways, thus, KYA1797K selectively regulates the Wnt/β-catenin and Ras/ERK pathways. KYA1797K enhances the β-catenin binding affinity of endogenous axin, GSK3β and β-TrCP. Interaction between APC and β-catenin is not enhanced by KYA1797K. It promotes the formation of the β-catenin destruction complex. KYA1797K degrades both β-catenin and Ras in these cells(CRC lines SW480, LoVo, DLD1 and HCT15) in a dose-dependent manner, cell proliferation is also suppressed by KYA1797K treatment. KYA1797K inhibits proliferation of CRC cells mainly via destabilization of β-catenin with additional Ras degradation. KYA1797K directly targeted axin and modulated conformation of the β-catenin destruction complex.
• Cell Research:
  To assay cell proliferation, HCT15 or SW480 cells are plated at a density of 2 × 104 cells/well, and D-WT or D-MT cells were seeded at a density of 1×104 cells/well in a 24-well plate. The cells are then treated with 25 μM KYA1797K or with control (DMSO) for 72 h. In a 96-well plate, cells are seeded at a density of 3 × 103 cells/well. After 24 h, the cells are treated with KY1220, KYA1797K, IWR-1 or XAV939 for 4 d. Next, MTT reagent is added to each well at a concentration of 0.25 mg/ml. After incubation for 2 h at 37°C, insoluble purple formazan is obtained by removing the medium and incubating in 1 ml (24-well) or 200 μl (96-well) of DMSO for 1 h. The absorbance of the formazan product is determined at 590 nm every 24 h. (Only for Reference)

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

betacatenin, Beta catenin, beta-catenin, bcatenin, inhibit, KYA1797K, KYA-1797K, Inhibitor, Wnt, Wnt/b-catenin, Wnt/betacatenin, Wnt/β-catenin, βcatenin, β-catenin

Compound Identifiers

PubChem CID

119057297