| 产品描述： | BC2059 is a small molecule inhibitor of the Wnt/beta-catenin pathway with potential antineoplastic activity. |
| 靶点： |
Wnt/beta-catenin |
| 体外研究： |
BC2059 induces apoptosis in primary multiple myeloma samples in vitro, causing minimal apoptosis on healthy peripheral blood mononuclear cells |
| 体内研究： |
BC2059 synergizes with the proteasome inhibitor bortezomib both in HMCL and primary multiple myeloma samples. Finally, in xenograft models of human myelomatosis, BC2059 delays tumor growth and prolongs survival with minor on-target side effects. Collectively, these results demonstrate the efficacy of targeting the Wnt/β-catenin pathway with BC2059 both in vitro and in vivo, at clinically achievable doses |
| 细胞实验： |
For β-catenin knockdown, 2 mL of 2 × 10^5/mL KMS18 cells were plated into a 12-well plate at day 0 (KMS18 doubling time: 36 hours).At day 1, media were replaced by 1 mL of Opti-MEM , and transfection was carried out with Lipofectamine RNAiMAX .For β-catenin knockdown, we used SignalSilence β-catenin siRNA I and β-catenin siRNA II (Cell Signaling Technology) at concentrations recommended by the manufacturer, whereas Silencer Negative Control No. 1 siRNA was used as a negative control, at the same concentration.Six hours after the transfection, 1 mL of fresh media (RPMI-10% FCS) was added in every well.At days 2 and 3, cells were treated with BC2059 (50, 100, 150 nmol/L) and then harvested at day 4 (72 hours after transfection).Cell death was monitored by PI staining with FACS, whereas untreated cells were collected for β-catenin protein level measurement by immunoblotting.Cells were lysed with RIPA lysis buffer, and 70 μg of protein was separated by 6% SDS-PAGE and blotted onto PVDF as already described.β-Acti |
| 动物实验： |
Adult age-matched Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were injected (intravenously) with 1 × 10^6 U266 HMCL, carrying the FUL2-TGvector .At day 21, a limited course of treatment was commenced after confirmation of established measurable disease by bioluminescence.Control mice (n = 4) received 17% Solutol HS 15 whereas treated mice received 5 (n = 4) or 10 mg/kg BC2059 (n = 5) twice a week intravenously for 3 consecutive weeks (6 doses in total).Tumor burden was monitored on a weekly basis by in vivo imaging, from the second week of the experiment (day 18) until the first mice reached scientific endpoints.Briefly, mice were anaesthetized, injected intraperitoneally with 125 mg/kg luciferin, and imaged with the Lumina III XR system.Acquisition and analysis were performed with the Living Image system.Peripheral blood counts were evaluated sequentially during the course of the experiment .Upon reaching scientific endpoints (hind limp paralysis, >20% weight loss), mice were humanely euthanized and tissues (skin and |
| 参考文献： |
1. Fiskus W, Sharma S, Saha S, et al. Pre-clinical efficacy of combined therapy with novel β-catenin antagonist BC2059 and histone deacetylase inhibitor against AML cells[J].Leukemia. 2015 Jun;29(6):1267-78 2. Savvidou I, Khong T, Cuddihy A, et al. Beta-catenin inhibitor BC2059 is efficacious as monotherapy or in combination with proteasome inhibitor bortezomib in multiple myeloma[J]. Molecular Cancer Therapeutics, 2017, 16(9):molcanther.0624.2016. |
| 溶解性： |
Soluble in DMSO |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.699 ml |
8.493 ml |
16.985 ml |
| 5 mM |
0.34 ml |
1.699 ml |
3.397 ml |
| 10 mM |
0.17 ml |
0.849 ml |
1.699 ml |
| 50 mM |
0.034 ml |
0.17 ml |
0.34 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京