Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update

Covalent inhibitors and other types of covalent modalities have seen a revival in the past two decades, with a variety of new targeted covalent drugs having been approved in recent years. A key feature of such molecules is an intrinsically reactive group, typically a weak electrophile, which enables the irreversible or reversible formation of a covalent bond with a specific amino acid of the target protein. This reactive group, often called the “warhead”, is a critical determinant of the ligand’s activity, selectivity, and general biological properties. In 2019, we summarized emerging and re-emerging warhead chemistries to target cysteine and other amino acids (Gehringer, M.; Laufer, S. A. J. Med. Chem. 2019,…

• BS
  Baden-Württemberg Stiftung
• FD
  Fonds der Chemischen Industrie
• DF
  Deutsche Forschungsgemeinschaft

  Awards: EXC 2180-390900677, 511101075
• SD
  Studienstiftung des Deutschen Volkes
• DM
  Dr. Mildred Scheel Stiftung für Krebsforschung