Powder: -20°C for 3 years | In solvent: -80°C for 1 year
ZW4864 is an orally active and selective β catenin/B-Cell lymphoma 9 protein protein interaction ( β catenin/BCL9 PPI ) inhibitor. ZW4864 inhibits β catenin/BCL9 PPI with a K i value of 0.76 μM and an IC 50 value of 0.87 μM.
产品描述 | ZW4864 is a selective inhibitor of the β-catenin/B-Cell Lymphoma 9 protein (β-catenin/BCL9 PPI) interaction, demonstrating oral activity. It inhibits β-catenin/BCL9 PPI with a K_i value of 0.76 μM and an IC_50 value of 0.87 μM. |
靶点活性 | β-catenin-BCL9:0.76 μM (Ki), β-catenin-BCL9:0.87 μM (IC50) |
体外活性 | ZW4864 (10~40 μM; 24 hours; SW480 and MBA-MD-231 cells) 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) 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) 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 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 dose-dependently suppresses β-catenin signaling activation, downregulates oncogenic β-catenin target genes, and abrogates invasiveness of β-catenin-dependent cancer cells. ZW4864 suppresses TOPFlash luciferase activities in β-catenin expressing HEK293 cells in a dose-dependent manner with an IC 50 of 11 μM. ZW4864 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 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. |
体内活性 | ZW4864 (20 mg/kg; p.o.) exhibits good pharmacokinetic properties with an oral bioavailability (F) of 83 %[1]. ZW4864 (90 mg/kg; p.o.) shows a variation in tumor growth in mice[1]. ZW4864 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. |
分子量 | 607.2 |
分子式 | C33H43ClN6O3 |
CAS No. | 2632259-93-7 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
ZW4864 2632259-93-7 ZW 4864 ZW-4864 Inhibitor inhibitor inhibit