| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 0.87 μM (β catenin/BCL9 PPI)[1]. Ki: 0.76 μM(β catenin/BCL9 PPI)[1]
ZW4864 targets the protein-protein interaction between β-catenin and B-cell lymphoma 9 (BCL9), a transcriptional coactivator that enhances β-catenin-mediated transcription. By inhibiting this interaction, ZW4864 prevents BCL9 from facilitating β-catenin-dependent transcription of target genes involved in cell proliferation and survival. The compound selectively disrupts the β-catenin/BCL9 PPI while sparing the β-catenin/E-cadherin interaction, demonstrating target selectivity. |
|---|---|
| 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].
ZW4864 inhibits β-catenin/BCL9 PPI with a Ki of 0.76 μM and an IC50 of 0.87 μM. It decreases the expression levels of β-catenin target genes Axin2 and cyclin D1 in SW480 and MDA-MB-231 cells. ZW4864 selectively triggers rapid apoptosis of triple-negative breast cancer cells with hyperactive β-catenin signaling while sparing normal mammary epithelial MCF10A cells. The compound suppresses the transcription of β-catenin target genes in a concentration-dependent manner without affecting the expression of the housekeeping gene HPRT. |
| 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].
In vivo activity data for ZW4864 are limited. As an orally active compound, it has potential for in vivo studies. By inhibiting β-catenin/BCL9 interaction, ZW4864 may suppress Wnt/β-catenin signaling and tumor growth in vivo. Further research is needed to evaluate its pharmacokinetic properties and efficacy in animal models of cancer, particularly in triple-negative breast cancer and other Wnt-driven malignancies. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for ZW4864 typically involves a protein-protein interaction assay to measure its ability to disrupt the β-catenin/BCL9 interaction. Recombinant β-catenin and BCL9 proteins are incubated with varying concentrations of ZW4864, and the interaction is measured using surface plasmon resonance (SPR), AlphaScreen, or ELISA-based methods. The compound's selectivity for the β-catenin/BCL9 interaction over the β-catenin/E-cadherin interaction is confirmed using similar assays.
|
| 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. The in vitro cellular assay for ZW4864 typically uses cancer cell lines with active β-catenin signaling, such as SW480, MDA-MB-231, and MDA-MB-468 cells. Cells are treated with varying concentrations of ZW4864 (10-40 μM; 24-72 hours). β-catenin target gene expression (Axin2, cyclin D1) is measured by qPCR or Western blot. Apoptosis is assessed using assays for caspase activation or Annexin V staining. Cell proliferation and viability are measured using standard assays such as MTT or CellTiter-Glo. |
| 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. In vivo animal studies for ZW4864 are not extensively documented. As an orally active compound, potential in vivo models include xenograft tumor models in mice, particularly using triple-negative breast cancer cell lines with hyperactive β-catenin signaling. Mice bearing subcutaneous tumors would be treated with ZW4864 via oral administration, and tumor growth inhibition, β-catenin target gene expression, and apoptosis markers would be assessed. However, specific protocols have not been reported. |
| ADME/Pharmacokinetics |
ZW4864 is an orally active compound. It has a molecular weight of 607.19 and a formula of C33H43ClN6O3. The compound is soluble in DMSO at 41.67 mg/mL (68.63 mM). Specific ADME parameters such as half-life, bioavailability, clearance, and volume of distribution are not detailed in the available literature. Researchers should perform their own pharmacokinetic studies if in vivo application is intended.
|
| Toxicity/Toxicokinetics |
Toxicity data for ZW4864 are not available in the public domain. As a research compound, comprehensive toxicological evaluations have not been performed. The compound is intended for laboratory research use only and should be handled with standard safety precautions. Appropriate personal protective equipment should be worn when handling this compound. Consult the Material Safety Data Sheet for specific safety and handling information.
|
| References | |
| Additional Infomation |
ZW4864 is an orally active, selective inhibitor of the β-catenin/BCL9 protein-protein interaction (Ki = 0.76 μM, IC50 = 0.87 μM). It selectively disrupts β-catenin/BCL9 binding while sparing β-catenin/E-cadherin interaction. ZW4864 decreases β-catenin target gene expression and triggers apoptosis in triple-negative breast cancer cells with hyperactive β-catenin signaling. The compound is not in clinical trials and has not been approved for therapeutic use. It remains a research tool for studying Wnt/β-catenin signaling and β-catenin/BCL9 biology.
|
| Molecular Formula |
C33H43CLN6O3
|
|---|---|
| Molecular Weight |
607.19
|
| Exact Mass |
606.308
|
| CAS # |
2632259-93-7
|
| Related CAS # |
ZW4864 free base;2632259-92-6
|
| PubChem CID |
164609513
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
43
|
| Complexity |
914
|
| Defined Atom Stereocenter Count |
1
|
| 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
|
| InChi Key |
PQRRIGABHUYXRQ-UFTMZEDQSA-N
|
| InChi Code |
InChI=1S/C33H42N6O3.ClH/c1-33(2,32(41)37-17-14-34-15-18-37)42-30-7-3-6-29(19-30)38-16-4-5-26(23-38)31(40)39(28-12-13-28)22-24-8-10-25(11-9-24)27-20-35-36-21-27;/h3,6-11,19-21,26,28,34H,4-5,12-18,22-23H2,1-2H3,(H,35,36);1H/t26-;/m1./s1
|
| Chemical Name |
(3R)-N-cyclopropyl-1-[3-(2-methyl-1-oxo-1-piperazin-1-ylpropan-2-yl)oxyphenyl]-N-[[4-(1H-pyrazol-4-yl)phenyl]methyl]piperidine-3-carboxamide;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 41.67 mg/mL (68.63 mM)
|
|---|---|
| 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
