The identification of cellular targets for small molecules, particularly those with an established clinical history, is pivotal for advancing our understanding of their therapeutic mechanisms and optimizing their clinical utility.[23, 34] Mei is a drug that has been used in the clinic for more than 30 years for the treatment of CML, yet its definitive molecular target remains elusive.[20c,d] In this study, we have identified the primary cellular target of Mei via ABPP and demonstrated that Mei binds covalently and reversibly to the Cys301 residue of PKMYT1. The gene discussed is PKMYT1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.