Summary

Emerging interest to harness the power of covalent inhibitors and the potential of making “undruggable” biological targets “druggable”, has led us to strategically establish experimental methods to evaluate covalent binders with the aim to support and drive future medicinal chemistry optimization strategies. We exemplified the application of – for chemists readily accessible – methods to assess, rank and predict the reactivity of Michael acceptors.

_{1 Evotec (UK) Ltd, 114 Innovation Drive, Milton Park, Abingdon OX14 4RZ, United Kingdom and University of Michigan, Departments of Medicinal Chemistry}

_{2 Pharmacology}

_{3 Internal Medicine - Division of Hematology-Oncology}

_{4) Ann Arbor, MI 48105, USA}