ZW4864 (free base) 是一种具有口服活性和选择性的 β catenin/ B-Cell lymphoma 9 蛋白-蛋白相互作用 (β catenin/BCL9 PPI) 抑制剂。ZW4864 (free base) 抑制β catenin/BCL9 PPI的Ki值为 0.76 μM，IC50值为 0.87 μM。
| 生物活性 | 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) inhibitsβ catenin/BCL9 PPIwith aKivalue of 0.76 μM and anIC50value of 0.87 μM[1]. |
| IC50& Target | IC50: 0.87 μM (β catenin/BCL9 PPI)[1].
Ki: 0.76 μM (β catenin/BCL9 PPI)[1] |
体外研究
(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 IC50of 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. |
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体内研究
(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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(175.22 mM;Need ultrasonic) 配制储备液 | 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 |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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