2632259-92-6
2632259-92-6 structure
- Name: ZW4864 free base
- Chemical Name: ZW4864 free base
- CAS Number: 2632259-92-6
- Molecular Formula: C33H42N6O3
- Molecular Weight: 570.72
- Catalog: Research Areas Cancer
- Create Date: 2021-10-19 20:38:37
- Modify Date: 2024-04-07 11:28:58
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ZW4864 (free base) is an orally active and selective β catenin/B-Cell lymphoma 9 protein−protein interaction (β catenin/BCL9 PPI) inhibitor. ZW4864 (free base) inhibits β catenin/BCL9 PPI with a Ki value of 0.76 μM and an IC50 value of 0.87 μM[1].
| Name | ZW4864 free base |
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| Description | ZW4864 (free base) is an orally active and selective β catenin/B-Cell lymphoma 9 protein−protein interaction (β catenin/BCL9 PPI) inhibitor. ZW4864 (free base) inhibits β catenin/BCL9 PPI with a Ki value of 0.76 μM and an IC50 value of 0.87 μM[1]. |
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| Related Catalog | |
| Target |
IC50: 0.87 μM (β catenin/BCL9 PPI)[1]. Ki: 0.76 μM (β catenin/BCL9 PPI)[1] |
| In Vitro | ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) (free base) decreases the expression levels of Axin2 and cyclin D1 proteins[1]. ZW4864 (10~40 μM; 72 hours; MDA-MB231, MCF10A and MDA-MB-468 cells) (free base) selectively triggeres rapid apoptosis of triple-negative breast cancer cells with hyperactive β-catenin signaling while sparing normal mammary epithelial MCF10A cells[1]. ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) (free base) suppresses 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[1]. ZW4864 (free base) binds with β-catenin and selectively disrupts the protein−protein interaction (PPI) between B-cell lymphoma 9 (BCL9) and β-catenin while sparing the β-catenin/E-cadherin PPI. ZW4864 (free base) dose-dependently suppresses β-catenin signaling activation, downregulates oncogenic β-catenin target genes, and abrogates invasiveness of β-catenin-dependent cancer cells. ZW4864 (free base) suppresses TOPFlash luciferase activities in β-catenin expressing HEK293 cells in a dose-dependent manner with an IC50 of 11 μM. ZW4864 (free base) also dose-dependently suppresses the TOPFlash luciferase activities in SW480 and Wnt 3a-activated MDA-MB-468 cells with the IC50s of 7.0 and 6.3 μM, respectively. ZW4864 (free base) selectively suppresses transactivation of β-catenin signaling[1]. Western Blot Analysis[1] Cell Line: SW480 and MBA-MD-231 cells Concentration: 10~40 μM Incubation Time: 24 hours Result: Decreased the expression levels of Axin2 and cyclin D1 proteins. Apoptosis Analysis[1] Cell Line: MDA-MB231, MCF10A and MDA-MB-468 cells Concentration: 10~40 μM Incubation Time: 72 hours Result: 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 Line: SW480 and MBA-MD-231 cells Concentration: 10~40 μM Incubation Time: 24 hours Result: 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. |
| In Vivo | ZW4864 (20 mg/kg; p.o.) (free base) exhibits good pharmacokinetic properties with an oral bioavailability (F) of 83 %[1]. ZW4864 (90 mg/kg; p.o.) (free base) shows a variation in tumor growth in mice[1]. ZW4864 (free base) shows good pharmacokinetic properties and effectively suppresses β-catenin target gene expression in the patient-derived xenograft mouse model[1]. Animal Model: C57BL/6 mice[1] Dosage: 20 mg/kg (Pharmacokinetic Analysis) Administration: P.o. Result: Exhibited good pharmacokinetic properties with an oral bioavailability (F) of 83%. Animal Model: Mice[1] Dosage: 90 mg/kg Administration: P.o. Result: Showed a variation in tumor growth in mice. |
| References |
| Molecular Formula | C33H42N6O3 |
|---|---|
| Molecular Weight | 570.72 |