Type III or allosteric kinase inhibitors for the treatment of non-small cell lung cancer.
Authors
Fasano, MDella Corte, C
Califano, Raffaele
Capuano, A
Troiani, T
Martinelli, E
Ciardiello, F
Morgillo, F
Affiliation
Second University of Naples, Medical Oncology, Department of Experimental and Internal Medicine "F. Magrassi e A. Lanzara" , Via S. Pansini 5, 80131 Napoli , Italia +39 081 5666745 ; +39 081 5666732 ;Issue Date
2014-06
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Show full item recordAbstract
In recent times, there has been much interest in the development of pharmacological kinase inhibitors that treat NSCLC. Furthermore, treatment options have been guided by the development of a wide panel of synthetic small molecule kinase inhibitors. Most of the molecules developed belong to the type I class of inhibitors that target the ATP-binding site in its active conformation. The high sequence similarity in the ATP-binding site among members of the kinase families often results in low selectivity and additional toxicities. Also, second mutations in the ATP-binding site, such as threonine to methionine at position 790, have been described as a mechanism of resistance to ATP-competitive kinase inhibitors. For these reasons, alternative drug development approaches targeting sites other than the ATP cleft are being pursued. The class III or allosteric inhibitors, which bind outside the ATP-binding site, have been shown to negatively modulate kinase activity.Citation
Type III or allosteric kinase inhibitors for the treatment of non-small cell lung cancer. 2014, 23 (6):809-21 Expert Opin Investig DrugsJournal
Expert Opinion on Investigational DrugsDOI
10.1517/13543784.2014.902934PubMed ID
24673358Type
ArticleLanguage
enISSN
1744-7658ae974a485f413a2113503eed53cd6c53
10.1517/13543784.2014.902934