A Fast Method to Monitor Tyrosine Kinase Inhibitor Mechanisms

  • J Med Chem. 2024 Nov 28;67(22):20571-20579. doi: 10.1021/acs.jmedchem.4c02042.
Alejandro Fernández  1  2 ,  Margarida Gairí  3 ,  María Teresa González  3 ,  Miquel Pons  1
Affiliations
  • 1. Biomolecular NMR Laboratory, Departament de Química Inorgànica i Orgànica, Universitat de Barcelona (UB), Baldiri Reixac 10-12, 08028 Barcelona. Spain.
  • 2. PhD Program in Biotechnology, Faculty of Pharmacy, Universitat de Barcelona (UB), 08028 Barcelona, Spain.
  • 3. Centres Científics i Tecnològics de La Universitat de Barcelona (CCiTUB), Baldiri Reixac 10-12, 08028 Barcelona. Spain.
PMID: 39513680 DOI: 10.1021/acs.jmedchem.4c02042
Abstract

Methionine residues within the kinase domain of Src serve as unique NMR probes capable of distinguishing between distinct conformational states of full-length Src, including alternative drug-inhibited forms. This approach offers a rapid method to differentiate between various inhibition mechanisms at any stage of drug development, eliminating the need to resolve the structure of Src-drug complexes. Using selectively 13C-methyl-enriched methionine, spectra can be acquired in under an hour, while natural abundance spectra with comparable information are achievable within a few hours.

Products