抄録
Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as “Austerity”. As a part of a research program aiming to develop a new-generation of anticancer agents, known as “anti-austerity agents”, guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity. These agents are able to exert preferential cytotoxic activity only under nutrient-deprived conditions with little or no toxicity under normal conditions. In the present study, a library of 14 GSDs was synthesized and screened against PANC-1 human pancreatic cells. Among tested compounds, GSD-11 showed the most potent activity with PC50 a value of 0.72 μM. It also inhibited pancreatic cancer cell migration and colony formation in a concentration-dependent manner. A mechanistic study revealed that this compound can inhibit the activation of the Akt/mTOR signaling pathway. Therefore, GSD-11 could be a promising lead compound for the anticancer drug discovery against pancreatic cancer.
本文言語 | 英語 |
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論文番号 | 116563 |
ジャーナル | Bioorganic and Medicinal Chemistry |
巻 | 54 |
DOI | |
出版ステータス | 出版済み - 2022/01/15 |
ASJC Scopus 主題領域
- 生化学
- 分子医療
- 分子生物学
- 薬科学
- 創薬
- 臨床生化学
- 有機化学