American Association for Cancer Research
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15357163mct160281-sup-166044_2_supp_3602848_3b03ml.pptx (69.59 kB)

AC0010 supplementary Figure 3 from AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients

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posted on 2023-04-03, 15:22 authored by Xiao Xu, Long Mao, Wanhong Xu, Wei Tang, Xiaoying Zhang, Biao Xi, Rongda Xu, Xin Fang, Jia Liu, Ce Fang, Li Zhao, Xiaobo Wang, Ji Jiang, Pei Hu, Hongyun Zhao, Li Zhang

AC0010 Supplementary Figure 3. Impact of AC0010 and gefitinib administration on tumor volumes

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China Twelfth Five-Year Plan

Hangzhou Municipal

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ARTICLE ABSTRACT

AC0010 is a pyrrolopyrimidine-based irreversible EGFR inhibitor, structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors, such as osimertinib and rociletinib. AC0010 selectively inhibits EGFR-active and T790M mutations with up to 298-fold increase in potency compared with wild-type EGFR. In a xenograft model, oral administration of AC0010 at a daily dose of 500 mg/kg resulted in complete remission of tumors with EGFR-active and T790M mutations for over 143 days with no weight loss. Three major metabolites of AC0010 were tested and showed no wild-type EGFR inhibition or off-target effects, such as inhibition of IGF-1R. AC0010 is safe in non–small cell lung cancer (NSCLC) patients at a dose range between 50 and 550 mg once per day, and no hyperglycemia or other severe adverse effects were detected, such as grade 3 QT prolongation. The objective responses were observed in NSCLC patients with EGFR T790M mutation. Mol Cancer Ther; 15(11); 2586–97. ©2016 AACR.

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