EGFR-IN-178 

EGFR-IN-178 is an orally active EGFR mutant inhibitor, exhibits highly selective inhibitory activity against mutants of the EGFR enzyme, including Del19 (IC₅₀ = 3.4 nM), L858R/T790 M (IC₅₀ = 2.9 nM), and Del19/T790 M (IC₅₀ = 2.5 nM). EGFR-IN-178 has good activity against JAK2 (IC₅₀ = 55.6 nM) and JAK3 (IC₅₀ = 46.1 nM) kinases. EGFR-IN-178 can increase cellular lipid oxide MDA, meanwhile decrease GSH content, causing ferroptosis in cancer cells. EGFR-IN-178 promotes apoptosis by increasing cleaved caspase-3 expression. EGFR-IN-178 can inhibit the phosphorylation of EGFR protein and decrease the active form p-JAK2 for JAK2, induce an increase in intracellular ROS. EGFR-IN-178 can be used for the study of non-small cell lung cancer (NSCLC)^[1].

EGFR-IN-178 (Compound 14a) (1-100 nM, pretreated for 72 hours, followed by culturing for 10–14 days) with IC₅₀ values of 18.5 nM for H1975-EGFR^L858R/T790M and 15.4 nM for PC9-EGFR^Del19, showing significant efficacy at 5 nM on PC9-EGFR^Del19 cells, at approximately 10 nM on H1975-EGFR^L858R/T790M cells, and no inhibition even at 100 nM on A549-EGFR^WT cells^[1].
EGFR-IN-178 (50-100 nM, 24 h) can enhance green fluorescence of H1975-EGFR^L858R/T790M cells, indicating that EGFR-IN-178 can lead to an increase in intracellular ROS^[1].
EGFR-IN-178 (10-100 nM) inhibits the phosphorylation of EGFR without reducing its total protein content in H1975-EGFR^L858R/T790M cells. It concurrently suppresses the JAK2-STAT3 signaling pathway by significantly decreasing p-JAK2 levels at 100 nM and p-STAT3 levels at 50 nM, which is consistent with its inhibitory effect on JAK2-3 kinase activity^[1].
EGFR-IN-178 (5-100 nM, 24 h) induces ferroptosis in H1975-EGFR^L858R/T790M cells, as evidenced by increased levels of lipid peroxides (MDA), iron ions (Fe²⁺), and oxidized lipids (green fluorescence), alongside decreased glutathione (GSH) and GPX4 levels, while it also promotes apoptosis by increasing cleaved caspase-3 expression^[1].
EGFR-IN-178 (10-50 nM, 12-24 h) can effectively inhibit the invasion and migration of H1975-EGFR^L858R/T790M cells in a concentration-dependent manner^[1].
EGFR-IN-178 shows no significant toxicity to HUVECs, HK-2, Hacat, and mouse-derived C2C12 (muscle tissue) and NIH3T3 (embryonic fibroblasts)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

EGFR-IN-178 (10 mg/kg, p.o., once daily for 13 days) exhibits potent antitumor activity, without significant weight loss, and no abnormalities in mental state, diet, or behavior in H1975-EGFR^L858R/T790M xenograft mice^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

463.54

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• [1]. Yao H, et al. The synthesis and evaluation of new N-(pyrazin-2-yl)-4-aminopyrimidine derivatives targeted EGFR and JAK. Eur J Med Chem. 2025 Dec 15;300:118120.