| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
IC50: 0.87 μM (β catenin/BCL9 PPI)[1]. Ki: 0.76 μM(β catenin/BCL9 PPI)[1]
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| ln Vitro |
ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) reduces the expression levels of Axin2 and cyclin D1 proteins [1]. ZW4864 (10~40 μM; 72 hours; MDA-MB231, MCF10A, and MDA-MB-468 cells) selectively triggers rapid apoptosis in triple-negative breast cancer cells with hyperactive β-catenin signaling while not Affects normal breast epithelial MCF10A cells [1]. ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) inhibits the transcription of β-catenin target genes in a concentration-dependent manner without affecting the expression of HPRT, a house-Keeper gene (in SW480 and Wnt 3a activated MDA-MB-231 cells) [1]. ZW4864 dose-dependently inhibits β-catenin signaling activation, downregulates oncogenic β-catenin target genes, and eliminates the invasiveness of β-catenin-dependent cancer cells. ZW4864 inhibits TOPFlash luciferase activity in β-catenin-expressing HEK293 cells in a dose-dependent manner with an IC50 of 11 μM. ZW4864 also dose-dependently inhibits TOPFlash luciferase activity in SW480- and Wnt 3a-activated MDA-MB-468 cells with IC50 of 7.0 and 6.3 μM, respectively. ZW4864 selectively inhibits transactivation of β-catenin signaling [1].
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| ln Vivo |
ZW4864 (20 mg/kg; po) has an oral bioavailability (F) of 83%, indicating acceptable pharmacokinetic characteristics[1]. ZW4864 demonstrates variability at 90 mg/kg; po[1]. In patient-derived xenograft mouse models, ZW4864 efficiently reduces the expression of the β-catenin target gene and demonstrates good pharmacokinetic qualities[1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: SW480 and MBA-MD-231 cells Tested Concentrations: 10~40 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished the expression levels of Axin2 and cyclin D1 proteins. Apoptosis Analysis[1] Cell Types: MDA -MB231, MCF10A and MDA-MB-468 cells Tested Concentrations: 10~40 μM Incubation Duration: 72 hrs (hours) Experimental Results: Selectively triggered rapid apoptosis of triple-negative breast cancer cells with hyperactive β-catenin signaling while sparing normal mammary epithelial MCF10A cells. RT-PCR[1] Cell Types: SW480 and MBA-MD-231 cells Tested Concentrations: 10~40 μM Incubation Duration: 24 hrs (hours) Experimental Results: Suppressed the transcription of β-catenin target genes in a concentration-dependent manner without affecting the expression of HPRT , a house-keeper gene, in both SW480 and Wnt 3a-activated MDA-MB-231 cells. |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice[1]
Doses: 20 mg/kg (pharmacokinetic/PK Analysis) Route of Administration: Po Experimental Results: demonstrated good pharmacokinetic/PK properties with an oral bioavailability (F) of 83%. Animal/Disease Models: Mice[1] Doses: 90 mg/kg Route of Administration: Po Experimental Results: demonstrated a variation in tumor growth in mice. |
| References |
[1]. Wang Z, et al. Discovery of an Orally Bioavailable Small-Molecule Inhibitor for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction. J Med Chem. 2021;64(16):12109-12131.
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| Molecular Formula |
C33H43CLN6O3
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|---|---|
| Molecular Weight |
607.19
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| CAS # |
2632259-93-7
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| Related CAS # |
ZW4864 free base;2632259-92-6
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| SMILES |
C1(N2C[C@H](C(=O)N(C3CC3)CC3C=CC(C4C=NNC=4)=CC=3)CCC2)=CC(OC(C)(C)C(=O)N2CCNCC2)=CC=C1.Cl
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 41.67 mg/mL (68.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6469 mL | 8.2347 mL | 16.4693 mL | |
| 5 mM | 0.3294 mL | 1.6469 mL | 3.2939 mL | |
| 10 mM | 0.1647 mL | 0.8235 mL | 1.6469 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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