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Title |
Study of the role of "gatekeeper" mutations V654A and T670I of c-kit kinase in the interaction with inhibitors by means mixed molecular dynamics/docking approach |
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Authors |
Marco Tutone*, Antonino Lauria, Anna Maria Almerico |
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Affiliation |
1Universita di Palermo, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO) - Sezione di Chimica Farmaceutica e Biologica, Via Archirafi 32 - 90123 Palermo.
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marco.tutone@unipa.it; *Corresponding author
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Article Type |
Hypothesis
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Date |
Received November 04, 2011; Accepted November 08, 2011; Published November 20, 2011
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Abstract |
The over-expression of c-kit proto-oncogene has been reported in hematopoietic cells, small cell lung cancer, and gastrointestinal stromal tumors. The clinical importance of c-kit expression in tumors focused the research towards inhibitors of this tyrosine kinase. Imatinib (Gleevec) was the first compound used in therapy, but mutations on c-kit led to reduced effectiveness or ineffectiveness of this treatment. Other compounds are likely to be effective against mutants, such as Sunitinib (Sutent), but the need for new and most effective inhibitors against mutants is still critical. We report mixed Molecular Dynamics/Docking study with the aim to unveil the molecular mechanism involved in the resistance of Imatinib, Sunitinib, and other known compounds against the "gatekeeper" mutants V654A e T670I. We tried to evidence strong and weak features of actual inhibitors in order to identify the guidelines to design new and most potent inhibitors against c-kit mutants.
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Citation |
Tutone et al.
Bioinformation 7(6): 296-298 (2011) |
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |