Discovery of potent small molecule ubiquitin-specific protease 10 inhibitors with anti-hepatocellular carcinoma activity through regulating YAP expression
文献类型：期刊论文
| Author | Lu, Yang10; Gao, Jian10; Wang, Peipei3,8,9 ; Chen, Haifeng10; He, Xinjun10; Luo, Mengxin10; Guo, Yu10; Li, Linjie10; Zhuang, Weihao10; Zhang, Bo1,2
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| Source | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| Issued Date | 2024-06-05 |
| Volume | 272Pages:21 |
| Keyword | Hepatocellular carcinoma Ubiquitin-specific protease 10 Deubiquitination Selectivity |
| ISSN | 0223-5234 |
| DOI | 10.1016/j.ejmech.2024.116468 |
| Corresponding Author | Dong, Xiaowu(dongxw@zju.edu.cn) ; Che, Jinxin(chejx@zju.edu.cn) |
| English Abstract | High expression of ubiquitin-specific protease 10 (USP10) promote the proliferation of hepatocellular carcinoma (HCC), thus the development of USP10 inhibitors holds promise as a novel therapeutic approach for HCC treatment. However, the development of selective USP10 inhibitor is still limited. In this study, we developed a novel USP10 inhibitor for investigating the feasibility of targeting USP10 for the treatment of HCC. Due to high USP10 inhibition potency and prominent selectivity, compound D1 bearing quinolin-4(1H)-one scaffold was identified as a lead compound. Subsequent research revealed that D1 significantly inhibits cell proliferation and clone formation in HCC cells. Mechanistic insights indicated that D1 targets the ubiquitin pathway, facilitating the degradation of YAP (Yes -associated protein), thereby triggering the downregulation of p53 and its downstream protein p21. Ultimately, this cascade leads to S -phase arrest in HCC cells, followed by cell apoptosis. Collectively, our findings highlight D1 as a promising starting point for USP10-positive HCC treatment, underscoring its potential as a vital tool for unraveling the functional intricacies of USP10. |
| WOS Keyword | USP10 ; P53 |
| Funding Project | National Natural Science Foundation of China[82173660] ; Natural Science Fund for Distinguished Young Scholars of Zhejiang Province[LR21H300003] ; Zhejiang Provincial Key Research & Development Plan[2023C03111] ; Zhejiang Provincial Key Research & Development Plan[2022C03155] ; Zhejiang Provincial Key Research & Development Plan[2023C03112] |
| WOS Research Area | Pharmacology & Pharmacy |
| Language | 英语 |
| WOS ID | WOS:001240368300004 |
| Publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311606]  |
| Collection | 中国科学院上海药物研究所 |
| Corresponding Author | Dong, Xiaowu; Che, Jinxin |
| Affiliation | 1.Zhejiang Univ, Sch Med, Canc Ctr, Hangzhou 310006, Zhejiang, Peoples R China 2.Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med,Dept Clin Pharmacol, Key Lab Clin Canc Pharmacol & Toxicol Res Zhejiang, Hangzhou 310006, Zhejiang, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Shanghai 528400, Guangdong, Peoples R China 5.Zhejiang Univ, Natl Key Lab Adv Drug Delivery & Release Syst, Hangzhou 310058, Peoples R China 6.Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China 7.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Pharm, Hangzhou 310009, Peoples R China 8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 10.Zhejiang Univ, Hangzhou Inst Innovat Med, Inst Drug Discovery & Design, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China |
| Recommended Citation GB/T 7714 | Lu, Yang,Gao, Jian,Wang, Peipei,et al. Discovery of potent small molecule ubiquitin-specific protease 10 inhibitors with anti-hepatocellular carcinoma activity through regulating YAP expression[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2024,272:21. |
| APA | Lu, Yang.,Gao, Jian.,Wang, Peipei.,Chen, Haifeng.,He, Xinjun.,...&Che, Jinxin.(2024).Discovery of potent small molecule ubiquitin-specific protease 10 inhibitors with anti-hepatocellular carcinoma activity through regulating YAP expression.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,272,21. |
| MLA | Lu, Yang,et al."Discovery of potent small molecule ubiquitin-specific protease 10 inhibitors with anti-hepatocellular carcinoma activity through regulating YAP expression".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 272(2024):21. |
入库方式： OAI收割
来源：上海药物研究所
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