Small Molecule SHP2 Inhibitor LXQ-217 affects Lung Cancer Cell Proliferation in Vitro and in Vivo
文献类型：期刊论文
| 作者 | Sun, Hao4; Bai, Xiaoyi4; Zhang, Yiting4; Gao, Yanan4; Dai, Jiajia2; Xing, Pan4; Zhu, Jiqiang1; Liu, Ruihua4; Wang, Zemin4; Li, Xiangqian3,4 |
| 刊名 | CHEMISTRY & BIODIVERSITY
 |
| 出版日期 | 2024-03-08 |
| 页码 | 11 |
| 关键词 | Anti-tumor SHP2 Orthosteric inhibitor Apoptosis Bromophenol |
| ISSN号 | 1612-1872 |
| DOI | 10.1002/cbdv.202301610 |
| 通讯作者 | Li, Xiangqian() |
| 英文摘要 | Background: SHP2 is highly expressed in a variety of cancer and has emerged as a potential target for cancer therapeutic agents. The identification of uncharged pTyr mimics is an important direction for the development of SHP2 orthosteric inhibitors.Methods: Surface plasmon resonance analysis and cellular thermal shift assay were employed to verify the direct binding of LXQ-217 to SHP2. The inhibitory effect of LXQ-217 was characterized by linear Weaver-Burke enzyme kinetic analysis and BIOVIA Discovery Studio. The inhibition of tumor cell proliferation by LXQ-217 was characterized by cell viability assay, colony formation assays and hoechst 33258 staining. The inhibition of lung cancer proliferation in vivo was studied in nude mice after oral administration of LXQ-217.Results: An electroneutral bromophenol derivative, LXQ-217, was identified as a competitive SHP2 inhibitor. LXQ-217 induced apoptosis and inhibited growth of human pulmonary epithelial cells by affecting the RAS-ERK and PI3 K-AKT signaling pathways. Long-term oral administration of LXQ-217 significantly inhibited the proliferation ability of lung cancer cells in nude mice. Moreover, mice administered LXQ-217 orally at high doses exhibited no mortality or significant changes in vital signs.Conclusions: Our findings on the uncharged orthosteric inhibitor provide a foundation for further development of a safe and effective anti-lung cancer drug. image |
| WOS关键词 | RESISTANCE |
| 资助项目 | National Natural Science Foundation of China ; Natural Science Foundation of Shandong Province[ZR2023MH245] ; Natural Science Foundation of Shandong Province[ZR2022QB090] ; Natural Science Foundation of Shandong Province[ZR2020QH364] ; National Key Research and Development Program of China[2022YFC2804105] ; Joint Fund of Shandong Natural Science Foundation[ZR2021LSW013] ; Qingdao Emerging Industry Cultivation Project[2023 (23-1-4-xxgg-19-nsh)] ; Special Research Assistant of Chinese Academy of Sciences[2022TSGC2204] ; [82003787] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001180672700001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://ir.qdio.ac.cn/handle/337002/184858]  |
| 专题 | 海洋研究所_海洋生态与环境科学重点实验室 |
| 通讯作者 | Li, Xiangqian |
| 作者单位 | 1.Shandong Linghai Biotechnol Co Ltd, Jinan 250299, Shandong, Peoples R China 2.Chinese Acad Sci, Key Lab Marine Ecol & Environm Sci, Inst Oceanol, Qingdao 266071, Shandong, Peoples R China 3.Lab Marine Drugs & Biol Prod, Natl Lab Marine Sci & Technol, Qingdao 266237, Shandong, Peoples R China 4.Shandong Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sun, Hao,Bai, Xiaoyi,Zhang, Yiting,et al. Small Molecule SHP2 Inhibitor LXQ-217 affects Lung Cancer Cell Proliferation in Vitro and in Vivo[J]. CHEMISTRY & BIODIVERSITY,2024:11. |
| APA | Sun, Hao.,Bai, Xiaoyi.,Zhang, Yiting.,Gao, Yanan.,Dai, Jiajia.,...&Li, Xiangqian.(2024).Small Molecule SHP2 Inhibitor LXQ-217 affects Lung Cancer Cell Proliferation in Vitro and in Vivo.CHEMISTRY & BIODIVERSITY,11. |
| MLA | Sun, Hao,et al."Small Molecule SHP2 Inhibitor LXQ-217 affects Lung Cancer Cell Proliferation in Vitro and in Vivo".CHEMISTRY & BIODIVERSITY (2024):11. |
入库方式： OAI收割
来源：海洋研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。