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 |
The free base ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) lowers the expression levels of the proteins Axin2 and cyclin D1 [1]. ZW4864 (10~40 μM; 72 hours; MDA-MB231, MCF10A, and MDA-MB-468 cells) (free base) preferentially induces hyperactive beta-catenin signaling-driven fast death in triple-negative breast cancer cells while sparing normal MCF10A breast epithelial cells [1]. ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) (free base) inhibited the transcription of β-catenin target genes in a concentration-dependent manner in both SW480 and Wnt 3a-activated MDA-MB-231 cells without changing the expression of the housekeeping gene HPRT [1]. Binding to β-catenin, ZW4864 (free base) specifically breaks down the protein-protein interaction (PPI) between β-catenin and B-cell lymphoma 9 (BCL9), leaving the β-catenin/E-cadherin PPI intact. ZW4864 is a free base that dose-dependently inhibits the activation of β-catenin signaling, downregulates the expression of oncogenic β-catenin target genes, and removes the invasiveness of cancer cells that rely on β-catenin. ZW4864 (free base) exhibits a dose-dependent inhibition of TOPFlash luciferase activity in HEK293 cells expressing β-catenin, with an IC50 of 11 μM. With an IC50 of 7.0 and 6.3 μM, respectively, ZW4864 (free base) also reduces TOPFlash luciferase activity in SW480- and Wnt 3a-activated MDA-MB-468 cells in a dose-dependent manner. ZW4864, a free base, inhibits β-catenin signaling transactivation specifically [1].
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ln Vivo |
Oral bioavailability (F) of ZW4864 (20 mg/kg; po) (free base) is 83%, indicating favorable pharmacokinetic features[1]. In mice, ZW4864 (90 mg/kg; po) (free base) exhibits alterations in tumor growth[1]. In patient-derived xenograft mouse models, ZW4864 free base efficiently suppresses β-catenin target gene expression and exhibits good pharmacokinetic characteristics[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 |
C33H42N6O3
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Molecular Weight |
570.72
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CAS # |
2632259-92-6
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Related CAS # |
ZW4864;2632259-93-7
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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
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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: 100 mg/mL (175.22 mM)
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7522 mL | 8.7609 mL | 17.5217 mL | |
5 mM | 0.3504 mL | 1.7522 mL | 3.5043 mL | |
10 mM | 0.1752 mL | 0.8761 mL | 1.7522 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.