Small Molecule SHP2 Inhibitor LXQ-217 affects Lung Cancer Cell Proliferation in Vitro and in Vivo

doi:10.1002/cbdv.202301610

	Small Molecule SHP2 Inhibitor LXQ-217 affects Lung Cancer Cell Proliferation in Vitro and in Vivo
	Sun, Hao 1; Bai, Xiaoyi 1; Zhang, Yiting 1; Gao, Yanan 1; Dai, Jiajia 3; Xing, Pan 1; Zhu, Jiqiang 4; Liu, Ruihua 1; Wang, Zemin 1; Li, Xiangqian 1,2
	2024-03-08
发表期刊	CHEMISTRY & BIODIVERSITY
ISSN	1612-1872
页码	11
通讯作者	Li, Xiangqian()
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
关键词	Anti-tumor SHP2 Orthosteric inhibitor Apoptosis Bromophenol
DOI	10.1002/cbdv.202301610
收录类别	SCI
语种	英语
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
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS记录号	WOS:001180672700001
出版者	WILEY-V C H VERLAG GMBH
WOS关键词	RESISTANCE
引用统计
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/184859
专题	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 Univ, State Key Lab Microbial Technol, Qingdao 266237, Shandong, Peoples R China 2.Lab Marine Drugs & Biol Prod, Natl Lab Marine Sci & Technol, Qingdao 266237, Shandong, Peoples R China 3.Chinese Acad Sci, Key Lab Marine Ecol & Environm Sci, Inst Oceanol, Qingdao 266071, Shandong, Peoples R China 4.Shandong Linghai Biotechnol Co Ltd, Jinan 250299, 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.