1. Development of the First Covalent Monopolar Spindle Kinase 1 (MPS1/TTK) Inhibitor
- Author
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Ricardo A. M. Serafim, André da Silva Santiago, Martin P. Schwalm, Zexi Hu, Caio V. dos Reis, Jessica E. Takarada, Priscila Mezzomo, Katlin B. Massirer, Mark Kudolo, Stefan Gerstenecker, Apirat Chaikuad, Lars Zender, Stefan Knapp, Stefan Laufer, Rafael M. Couñago, and Matthias Gehringer
- Subjects
Male ,Models, Molecular ,Antineoplastic Agents ,Cell Cycle Proteins ,Triple Negative Breast Neoplasms ,In Vitro Techniques ,Protein Serine-Threonine Kinases ,Protein-Tyrosine Kinases ,Crystallography, X-Ray ,Mass Spectrometry ,Mice ,Cell Line, Tumor ,Drug Design ,Drug Discovery ,Microsomes, Liver ,Animals ,Humans ,Molecular Medicine ,Female ,Drug Screening Assays, Antitumor ,Protein Kinase Inhibitors - Abstract
Monopolar spindle kinase 1 (MPS1/TTK) is a key element of the mitotic checkpoint and clinically evaluated as a target in the treatment of aggressive tumors such as triple-negative breast cancer. While long drug-target residence times have been suggested to be beneficial in the context of therapeutic MPS1 inhibition, no irreversible inhibitors have been reported. Here we present the design and characterization of the first irreversible covalent MPS1 inhibitor
- Published
- 2022
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