YB-0158 被称为 Wnt 通路抑制剂 2。
YB-0158 is known as Wnt pathway inhibitor 2. YB-0158 is a peptidomimetic structure with high predicted affinity for Sam68 [1].
YB-0158 elicits a cancer-selective response impeding main cancer stem cell hallmarks [1].
YB-0158 displayed enhanced selective toxicity in colorectal cancer models vs. normal intestinal epithelium progenitor cells. YB-0158 exert negative impact on cancer cell growth by inducing apoptosis and reducing proliferation. YB-0158 eradicated CSCs activity in vivo by a syngeneic mouse-to-mouse serial transplantation assay [2].
参考文献:
[1]. Angelique N. Masibag, Christopher J. Bergin, Joshua R. Haebe, A?cha Zouggar, Muhammad S. Shah, Tamara Sandouka, Amanda Mendes da Silva, Fran?ois M. Desrochers, Aube Fournier-Morin, Yannick D. Benoit.Pharmacological targeting of Sam68 functions in colorectal cancer stem cells. iScience, Volume 24, Issue 12, 17 December 2021, Pages 103442
[2]. Masibag, Angelique Noelline. Characterization of a New Peptidomimetic Compound Modulating Sam68 Functions in Human Colon Cancer Stem Cells. Diss. Université d'Ottawa/University of Ottawa, 2021.
YB-0158 被称为 Wnt 通路抑制剂 2。YB-0158 是一种拟肽结构，对 Sam68 [1] 具有高预测亲和力。
YB-0158 引发癌症选择性反应，阻碍主要的癌症干细胞标志[1]。
与正常肠上皮祖细胞相比，YB-0158 在结直肠癌模型中表现出增强的选择性毒性。 YB-0158 通过诱导细胞凋亡和减少增殖对癌细胞生长产生负面影响。 YB-0158 通过同源小鼠对小鼠连续移植试验在体内根除 CSCs 活性[2]。
| Cell experiment [1]: | |
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Cell lines |
HT29 cells |
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Preparation Method |
Cells were treated with DMSO or YB-0158 for 48 hours. As a positive control, each cell line was treated with 1 μM of staurosporine for 6 h. |
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Reaction Conditions |
0.2, 0.5μM for 48 hours |
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Applications |
EdU incorporation confirmed that lower doses of YB-0158 were sufficient to significantly decrease proliferation in human CRC cells. When used at 0.5 μM, YB-0158 also significantly increased apoptosis in CRC cells as represented by activated Caspase-3/7 detection assays |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice accepted subcutaneous injection of MC38 cells into the flanks |
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Preparation Method |
Seven days post-injection, daily doses of YB-0158 (100mg/kg), or control saline (HBSS vehicle) were intraperitoneally injected in tumor-bearing animals for 14 days. |
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Dosage form |
Intraperitoneal injection, 100mg/kg |
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Applications |
No significant differences in primary tumor size were observed upon either YB-0158 in vivo treatments versus saline controls, residual secondary tumors from YB-0158-treated group were significantly smaller versus matched saline controls. |
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参考文献: [1]: Angelique N. Masibag, Christopher J. Bergin, Joshua R. Haebe, A?cha Zouggar, Muhammad S. Shah, Tamara Sandouka, Amanda Mendes da Silva, Fran?ois M. Desrochers, Aube Fournier-Morin, Yannick D. Benoit.Pharmacological targeting of Sam68 functions in colorectal cancer stem cells. iScience, Volume 24, Issue 12, 17 December 2021, Pages 103442 | |
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