ZW4864 free base

SKU: orb1685261

Description

ZW4864 (free base) is an orally bioavailable small molecule that selectively inhibits the β-catenin/BCL9 protein-protein interaction with a Kᵢ of 0.76 µM. This inhibitor is a valuable research tool for studying Wnt/β-catenin signaling in oncology, suitable for both in vitro biochemical assays and in vivo pharmacokinetic studies.

Research Area

Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 2632259-92-6
• MW: 570.72
• Purity: 99.81% (May vary between batches)
• Formula: C₃₃H₄₂N₆O₃
• SMILES: CC(C)(Oc1cccc(c1)N1CCC[C@H](C1)C(=O)N(Cc1ccc(cc1)-c1cn[nH]c1)C1CC1)C(=O)N1CCNCC1
• Target: Wnt/beta-catenin
• Solubility: DMSO:90 mg/mL (157.7 mM)

Bioactivity

• In Vivo:
  Administered orally at a dosage of 20 mg/kg, ZW4864 (free base) displays favorable pharmacokinetic properties, achieving an oral bioavailability of 83% in C57BL/6 mice . At a higher dosage of 90 mg/kg, also administered orally, it demonstrates the ability to influence tumor growth in mice . Additionally, ZW4864 (free base) effectively inhibits β-catenin target gene expression in a patient-derived xenograft mouse model, further indicating its potential therapeutic benefits .
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• In Vitro:
  ZW4864 (10~40 μM; free base) demonstrates a multifaceted inhibitory effect on β-catenin signaling pathways in various cancer cell lines. Over 24 hours, it diminishes Axin2 and cyclin D1 protein levels in SW480 and MDA-MB-231 cells, and selectively induces apoptosis in triple-negative breast cancer cells (MDA-MB231, MDA-MB-468) with hyperactive β-catenin, sparing normal MCF10A cells, over 72 hours. It also decreases the transcription of β-catenin target genes without affecting HPRT expression, indicating specificity in its action. By binding to β-catenin, ZW4864 disrupts its interaction with BCL9 but not with E-cadherin, thereby selectively targeting β-catenin's oncogenic activity. This compound efficaciously suppresses β-catenin-dependent signaling and invasiveness of cancer cells, as well as TOPFlash luciferase activity in a dose-dependent manner, showing particular potency with IC50 values ranging from 6.3 to 11 μM across different cell lines. Collectively, these findings underscore ZW4864's potential as a targeted therapeutic agent against β-catenin-dependent malignancies.
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Storage & Handling

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

Alternative Names

betacatenin, beta-catenin, bcatenin, Wnt/betacatenin, Wnt/b-catenin, Wnt, Wnt/β-catenin, βcatenin, β-catenin, ZW4864 free base, ZW4864, ZW-4864, ZW 4864

Compound Identifiers

PubChem CID

156180089