Zehe Ge, Miao Xu, Yuqian Ge, Guang Huang, Dongyin Chen, Xiuquan Ye, Yibei Xiao, Hongyu Zhu, Rong Yin, Hua Shen, Gaoxiang Ma, Lianwen Qi, Guining Wei, Dongmei Li, Shaofeng Wei, Meng Zhu, Hongxia Ma, Zhumei Shi, Xiuxing Wang, Xin Ge, Xu Qian
EGFRT790M mutation causes resistance to the first-generation tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, the therapeutic options for sensitizing first TKIs and delaying the emergence of EGFRT790M mutant are limited. In this study, we show that quercetin directly binds with glucose-6-phosphate dehydrogenase (G6PD) and inhibits its enzymatic activity through competitively abrogating NADP+ binding in the catalytic domain. This inhibition subsequently reduces intracellular NADPH levels, resulting in insufficient substrate for methionine reductase A (MsrA) to reduce M790 oxidization of EGFRT790M and inducing the degradation of EGFRT790M ...
November 10, 2023: Cell Reports