- A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/β-catenin signaling pathway
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Cancer stem cells (CSCs) are responsible for carcinogenesis, cancer progression, relapse, metastasis and drug resistance. Therefore, the development of drug molecules targeting CSCs plays a vital role in medicinal researching field. However, there are extremely rare molecules that selectively ablate CSCs. The research and development of drugs targeting CSCs is limited due to a lack of anti-CSCs lead compounds. In this study, an anti-CSCs lead compound 35b was discovered, which was derived from the natural chemical scaffold of Symplostatin 4. This compound exhibited a significantly suppressive effect on tumor growth both in vitro and in vivo. Additionally, 35b could significantly reduce the number of melanoma tumor spheres and decrease the percentage of ALDH+ melanoma cells. Further mechanism study illustrated that compound 35b could eliminate the melanoma CSCs by efficiently blocking Wnt/β-catenin signaling pathway. Collectively, our findings would provide a novel chemical scaffold and alternative idea of molecular design for development of anti-CSCs drugs.
- Liu, Shuangwei,Gao, Xian,Zhang, Lisong,Qin, Shuanglin,Wei, Mingming,Liu, Ning,Zhao, Rui,Li, Benlong,Meng, Ye,Lin, Gang,Lu, Cheng,Liu, Xinhua,Xie, Maodun,Liu, Tongtong,Zhou, Honggang,Qi, Min,Yang, Guang,Yang, Cheng
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- Design and synthesis of dual inhibitors for matrix metalloproteinase and cathepsin
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The first example of dual inhibitors for matrix metalloproteinase (MMP) and cathepsin is described. An appropriate alignment of peptide-parts and two different specific functional groups in one molecule led to the discovery of a potent dual inhibitor (3a)
- Yamamoto, Minoru,Ikeda, Shoji,Kondo, Hirosato,Inoue, Shintaro
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p. 375 - 378
(2007/10/03)
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