A Fast Method to Monitor Tyrosine Kinase Inhibitor Mechanisms
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 <sup>13</sup>C-methyl-enriched methionine, spectra can be acquired in under an hour, while natural abundance spectra with comparable information are achievable within a few hours.
Authors
- Miquel Pons (ORCID: https://orcid.org/0000-0002-0586-8322)
- M. Teresa González (ORCID: https://orcid.org/0000-0002-7253-797X)
- Alejandro Fernández (ORCID: https://orcid.org/0000-0002-4163-2202)
- Margarida Gairí (ORCID: https://orcid.org/0000-0003-3560-5897)
Institutions
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2024-11-08
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c02042
- Citations
- 2
- Primary Topic
- Chronic Myeloid Leukemia Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.91
Funders
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- Generalitat de Catalunya
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Agencia Estatal de Investigación