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Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer

文献类型：期刊论文

作者Guo, Zhong-Qiang4,6,7; Zheng, Tong5,8; Chen, Baoen5; Luo, Cheng9; Ouyang, Sisheng9; Gong, Shouzhe5; Li, Jiafei5; Mao, Liu-Liang10; Lian, Fulin11; Yang, Yong12
刊名CANCER CELL
出版日期2016-09-12
卷号30期号:3页码:474-484
ISSN号1535-6108
DOI10.1016/j.ccell.2016.08.003
文献子类Article
英文摘要In the cytoplasm of virtually all clear-cell renal cell carcinoma (ccRCC), speckle-type POZ protein (SPOP) is overexpressed and misallocated, which may induce proliferation and promote kidney tumorigenesis. In normal cells, however, SPOP is located in the nucleus and induces apoptosis. Here we show that a structure-based design and subsequent hit optimization yield small molecules that can inhibit the SPOP-substrate protein interaction and can suppress oncogenic SPOP-signaling pathways. These inhibitors kill human ccRCC cells that are dependent on oncogenic cytoplasmic SPOP. Notably, these inhibitors minimally affect the viability of other cells in which SPOP is not accumulated in the cytoplasm. Our findings validate the SPOP-substrate protein interaction as an attractive target specific to ccRCC that may yield novel drug discovery efforts.
WOS关键词UBIQUITIN-PROTEASOME PATHWAY ; RENAL-CELL CARCINOMA ; PROSTATE-CANCER ; CLINICAL-TRIALS ; PROTEIN ; INHIBITORS ; INACTIVATION ; DEGRADATION ; SPECIFICITY ; COMPLEX
WOS研究方向Oncology ; Cell Biology
语种英语
WOS记录号WOS:000383314200012
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/275894]  
专题药理学第三研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
药物发现与设计中心
通讯作者Yang, Cai-Guang; Liu, Jiang; Jiang, Hualiang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China;
2.Beijing Normal Univ, Coll Life Sci, Beijing 100875, Peoples R China
3.Beijing Normal Univ, Minist Educ, Key Lab Cell Proliferat & Regulat Biol, Beijing 100875, Peoples R China;
4.Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genome Sci & Informat, Beijing 100101, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, Biol Chem Lab, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
6.Peking Univ, Dept Urol, Hosp 1, Beijing 100034, Peoples R China;
7.Wuhan Univ, Dept Urol, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China;
8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
9.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
10.Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China;
推荐引用方式
GB/T 7714		 Guo, Zhong-Qiang,Zheng, Tong,Chen, Baoen,et al. Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer[J]. CANCER CELL,2016,30(3):474-484.
APA Guo, Zhong-Qiang.,Zheng, Tong.,Chen, Baoen.,Luo, Cheng.,Ouyang, Sisheng.,...&Jiang, Hualiang.(2016).Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer.CANCER CELL,30(3),474-484.
MLA Guo, Zhong-Qiang,et al."Small-Molecule Targeting of E3 Ligase Adaptor SPOP in Kidney Cancer".CANCER CELL 30.3(2016):474-484.

入库方式： OAI收割

来源：上海药物研究所

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