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Can I read Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFRL858R/T790M mutation on EtoBox?
Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFRL858R/T790M mutation by Lumei Dai; Feng Qin; Yuying Xie; Bin Zhang; Zhijie Zhang; Sijia Liang; Fujia Chen; Xiaochao Huang; Hengshan Wang is a Chemistry article available to read on EtoBox.
What is Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFRL858R/T790M mutation about?
Dual- or multi-targeted EGFR inhibitors as single drugs can overcome EGFR inhibitor resistance and circumvent many disadvantages of combination therapy. In this work, fifteen 4-anilinoquinazoline derivatives bearing nitrogen mustard or hemi mustard moieties were designed and synthesized as dual EGFR-DNA targeting anticancer agents. Structures of target molecules were confirmed by 1H NMR, 13C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Compound 6g emerged as the most potent derivative against mutant-type H1975 cells with IC50 value of 1.45 μM, which exhibited 4-fold stronger potency than Chl/Gef (equimolar combination of chlorambucil and gefitinib). Kinase inhibition studies indicated that 6g showed excellent inhibitory effect on EGFRL858R/T790M enzyme, which was 8.6 times more effective than gefitinib. Mechanistic studies indicated that 6g induced apoptosis of H1975 cells in a dose-dependent manner and caused DNA damage. Importantly, 6g could significantly inhibit the expression of p-EGFR and its downstream p-AKT and p-ERK in H1975 cells. Molecular docking was also performed to gain insights into the ligand-binding interactions of
Who reads Antitumor activity and mechanisms of dual EGFR/DNA-targeting strategy for the treatment of lung cancer with EGFRL858R/T790M mutation?
It is typically read by researchers, students, and practitioners in Chemistry.
- Author
- Lumei Dai; Feng Qin; Yuying Xie; Bin Zhang; Zhijie Zhang; Sijia Liang; Fujia Chen; Xiaochao Huang; Hengshan Wang
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Chemistry (Physical Sciences)