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您的检索式：作者名="Changkai Jia"
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| 1 | Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations显示文摘Various c-mesenchymal-to-epithelial transition(c-MET) inhibitors are effective in the treatment of non-small cell lung cancer;however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras(PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC_(50) values and achieved picomolar DC_(50) values and>99% of maximum degradation(D_(max)) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion.Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^(Y1230H) and c-MET^(D1228N) mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations. | Pengyun Li Changkai Jia Zhiya Fan Xiaotong Hu Wenjuan Zhang Ke Liu Shiyang Sun Haoxin Guo Ning Yang Maoxiang Zhu Xiaomei Zhuang Junhai Xiao Zhibing Zheng Song Li | 2023 | Acta Pharmaceutica Sinica B2023，13，6： | 0 |
| 2 | Research Progress of Noninvasive Diagnostic Methods for Nonalcoholic Steatohepatitis显示文摘Distinguishing between nonalcoholic steatohepatitis(NASH) and advanced liver fibrosis is the key for clinical diagnosis of non-alcoholic fatty liver disease(NAFLD). Liver biopsy, which is widely used for diagnosis of liver diseases at present, has many drawbacks, such as being invasive, expensive and unstable. This article compares and summarizes the commonly used non-invasive diagnostic methods, including their diagnostic parameters, advantages and disadvantages, in order to provide a useful reference for the diagnosis of NASH. | Yishi JIA Changkai ZHOU Ci SONG | 2023 | Agricultural Biotechnology2023，12，3： | 0 |
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