The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Cysteine Mapping in Conformationally Distinct Kinase Nucleotide Binding Sites: Application to the Design of Selective Covalent Inhibitors
Open accessAbstract
Kinases have emerged as one of the most prolific therapeutic targets. An important criterion in the therapeutic success of inhibitors targeting the nucleotide binding pocket of kinases is the inhibitor residence time. Recently, covalent kinase inhibitors have attracted attention since they confer terminal inhibition and should thus be more effective than reversible inhibitors with transient inhibition. The most robust approach to design irreversible inhibitors is to capitalize on the nucleophilicity of a cysteine thiol group present in the target protein. Herein, we report a systematic analysis of cysteine residues present in the nucleotide binding site of kinases, which could be harnessed for irreversible inhibition, taking into consideration the different kinase conformations. We demonstrate the predictive power of this analysis with the design and validation of an irreversible inhibitor of KIT/PDGFR kinases. This is the first example of a covalent kinase inhibitor that combines a pharmacophore addressing the DFG-out conformation with a covalent trap.
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The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
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Drug-target residence time and its implications for lead optimization
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Novel mutant-selective EGFR kinase inhibitors against EGFR T790M
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ERK1/2 MAP kinases: Structure, function, and regulation
Roskoski, R. (2012) · Pharmacological Research · doi:10.1016/j.phrs.2012.04.005 · Cited by 1,650
Kinase-targeted cancer therapies: progress, challenges and future directions
Bhullar, K. S., Lagarón, N. O., McGowan, E. M., Parmar, I., Jha, A., Hubbard, B. P., & Rupasinghe, H. P. V. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0804-2 · Cited by 1,245
Targeted Covalent Inhibitors for Drug Design
Baillie, T. A. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201601091 · Cited by 578
Small-molecule kinase inhibitors: an analysis of FDA-approved drugs
Wu, P., Nielsen, T. E., & Clausen, M. H. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2015.07.008 · Cited by 457
Prolonged and tunable residence time using reversible covalent kinase inhibitors
Bradshaw, J. M., McFarland, J. M., Paavilainen, V. O., Bisconte, A., Tam, D., Phan, V. T., Romanov, S., Finkle, D., Shu, J., Patel, V., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1817 · Cited by 422
Metadata
- Authors
- Leproult, E., Barluenga, S., Moras, D., Wurtz, J.-M., & Winssinger, N.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-02-15
- Volume
- 54
- Issue
- 5
- Pages
- 1347-1355
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2071648775
- Cited by
- 193
- References
- 8
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- green
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- Leproult, E., Barluenga, S., Moras, D., Wurtz, J.-M., & Winssinger, N. (2011). Cysteine Mapping in Conformationally Distinct Kinase Nucleotide Binding Sites: Application to the Design of Selective Covalent Inhibitors. Journal of Medicinal Chemistry. https://doi.org/10.1021/jm101396q
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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