Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2

作     者：Penglei Wang Xuechao Jia Bingbing Lu Han Huang Jialin Liu Xuejiao Liu Qiong Wu Yamei Hu Pan Li Huifang Wei Tingting Liu Dengyun Zhao Lingwei Zhang Xueli Tian Yanan Jiang Yan Qiao Wenna Nie Xinli Ma Ruihua Bai Cong Peng Zigang Dong Kangdong Liu Penglei Wang;Xuechao Jia;Bingbing Lu;Han Huang;Jialin Liu;Xuejiao Liu;Qiong Wu;Yamei Hu;Pan Li;Huifang Wei;Tingting Liu;Dengyun Zhao;Lingwei Zhang;Xueli Tian;Yanan Jiang;Yan Qiao;Wenna Nie;Xinli Ma;Ruihua Bai;Cong Peng;Zigang Dong;Kangdong Liu

作者机构：Department of PathophysiologyBasic Medicine Research CenterSchool of Basic Medical SciencesAMSZhengzhou University450000 ZhengzhouChina China-US(Henan)Hormel Cancer Institute450000 ZhengzhouChina The Department of PathologyAffiliated Cancer Hospital of Zhengzhou University450000 ZhengzhouChina The Department of DermatologyXiangya HospitalCentral South University410078 ChangshaChina The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention450000 ZhengzhouChina State Key Laboratory of Esophageal Cancer Prevention and TreatmentZhengzhou University450000 ZhengzhouChina Provincial Cooperative Innovation Center for Cancer ChemopreventionZhengzhou UniversityZhengzhouChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2023年第8卷第4期

页      面：1874-1888页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the National Natural Science Foundations of China(No.81872335) The Central Plains Science and Technology Innovation Leading Talents(No.224200510015) Program for Science&Technology Innovation Talents in Universities of Henan(No.20HASTIT048) the Cultivation Foundation of Zhengzhou University(No.JC202035022) 

主　　题：MEK1/2 BRAF activation 

摘      要：Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic *** of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising *** this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS *** enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/*** assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase ***,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase ***,erianin attenuated melanoma and colorectal cancer in ***,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.