K-756

SKU: orb1308164

Description

K-756 is a potent and selective tankyrase (TNKS) inhibitor, exhibiting IC50 values of 31 nM and 36 nM against TNKS1 and TNKS2, respectively. This small molecule is a valuable research tool for studying Wnt/β-catenin signaling in cancer biology and has been utilized in both cellular and in vivo models to investigate pathway inhibition.

Research Area

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

Key Properties

• CAS Number: 130017-40-2
• MW: 433.5
• Purity: 99.68% (May vary between batches)
• Formula: C₂₄H₂₇N₅O₃
• SMILES: COc1cc2ncnc(N3CCC(CN4Cc5ccccc5NC4=O)CC3)c2cc1OC
• Target: Wnt/beta-catenin|||PARP
• Solubility: DMSO:4.5 mg/mL (10.38 mM)

Bioactivity

• Target IC50:
  TNKS2:36 nM|TNKS1:31 nM
• In Vivo:
  Vehicle (0.5% MC400) or K-756 is given orally once daily for three consecutive days at doses of 100, 200, and 400 mg/kg. The inhibition of the Wnt/β-catenin pathway in tumors is assessed by measuring the levels of FGF20 and LGR5, as well as luciferase activity. Inhibition of the Wnt/β-catenin pathway is evident at a 400 mg/kg dose after just one day of administration. After three days of treatment, significant reductions in FGF20 expression and reporter activity are observed at doses of 100 mg/kg and higher, while LGR5 expression significantly decreases at doses of 200 mg/kg and higher. The greatest inhibitory effect is achieved with a three-day administration of K-756 at 400 mg/kg .
  Read more...
• In Vitro:
  K-756 inhibits the cell growth of APC-mutant colorectal cancer COLO 320DM and SW403 cells by inhibiting the Wnt/β-catenin pathway. K-756 is a novel and selective Wnt/β-catenin pathway inhibitor targeting tankyrase (TNKS). TNKS is one of the members of the PARP family. K-756 binds to the induced pocket of TNKS and inhibits its enzyme activity. K-756 inhibits TNKS1 and TNKS2 by 97% and 100%, respectively. The inhibitory activity of K-756 against PARP1, PARP2, PARP3, PARP6, PARP7, and PARP11 is less than 13%. K-756 strongly inhibits the reporter activity in DLD-1/TCF-Luc cells (IC50: 110 nM) but does not inhibit DLD-1/mtTCF-Luc cells, even at 1,000 nM. APC-mutant colorectal cancer cell line COLO 320DM and SW403 cells are treated with K-756 and after 144 hours, cell growth inhibition is measured by an XTT assay. The application of K-756 inhibits the cell growth of COLO 320DM with a GI50 of 780 nM. K-756 also inhibits SW403 with a GI50 of 270 nM.
  Read more...

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

bcatenin, beta-catenin, betacatenin, K 756, K-756, K756, Inhibitor, inhibit, PARP, TNKS1, TNKS2, Wnt, Wnt/b-catenin, Wnt/betacatenin, Wnt/β-catenin, poly ADP ribose polymerase, βcatenin

Compound Identifiers

PubChem CID

14668434