Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells

•CRISPR/Cas9 knockout screen identifies COPB2 as the EMI1 top resistance gene.•EMI66 alters the electrophoretic mobility of COPB2 and downregulate RTK expression.•EMI66 alters EGFR and COPB2 subcellular localization.•COPB2 suppression alters ER stress response and RTK post-translational processing.•EMI66 blocks proliferation of lung cancer cells and primary lung cancer organoids.