ZW4864 free base

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 K i value of 0.76 μM and an IC 50 value of 0.87 μM 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. 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. 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. 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 IC 50 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 IC 50 s of 7.0 and 6.3 μM, respectively. ZW4864 (free base) selectively suppresses transactivation of β-catenin signaling. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell 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 AnalysisCell 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-PCRCell 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 % . ZW4864 (90 mg/kg; p.o.) (free base) shows a variation in tumor growth in mice . ZW4864 (free base) shows good pharmacokinetic properties and effectively suppresses β-catenin target gene expression in the patient-derived xenograft mouse model . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: C57BL/6 mice Dosage: 20 mg/kg (Pharmacokinetic Analysis) Administration: P.o. Result: Exhibited good pharmacokinetic properties with an oral bioavailability (F) of 83%. Animal Model: Mice Dosage: 90 mg/kg Administration: P.o. Result: Showed a variation in tumor growth in mice. Form:Solid IC50& Target:IC50: 0.87 μM (β catenin/BCL9 PPI),Ki: 0.76 μM (β catenin/BCL9 PPI)

No numbering system information yet

No physical and chemical property information yet

No safety information yet

No production method and use information yet

No upstream information yet

No downstream information yet

No related product information yet