Efficacy of iron(II)-targeted forms of FDA-approved MEK inhibitor cobimetinib. A. Structure of TRX-DRUG conjugates such as TRX-COBI, which releases free cobimetinib upon reaction with Fe2+. B. Tumor volume over time in mice bearing KRAS lung adenocarcinoma and treated with vehicle, SHP2 inhibitor + cobimetinib, or SHP2i + TRX-COBI at equivalent, equimolar doses. C. Phospho-ERK staining of tumor in spleen from animals studied in panel B, indicating selective activation of TRX-COBI in tumor. Unpublished data reproduced from bioRxiv 2020.05.12.088971.