Type III or allosteric kinase inhibitors for the treatment of non-small cell lung cancer.
Della Corte, C
AffiliationSecond 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 ;
MetadataShow full item record
AbstractIn 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.
CitationType III or allosteric kinase inhibitors for the treatment of non-small cell lung cancer. 2014, 23 (6):809-21 Expert Opin Investig Drugs
JournalExpert Opinion on Investigational Drugs
- Allosteric small-molecule kinase inhibitors.
- Authors: Wu P, Clausen MH, Nielsen TE
- Issue date: 2015 Dec
- Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: comparative pharmacokinetics and drug-drug interactions.
- Authors: Peters S, Zimmermann S, Adjei AA
- Issue date: 2014 Sep
- Preclinical rationale for PI3K/Akt/mTOR pathway inhibitors as therapy for epidermal growth factor receptor inhibitor-resistant non-small-cell lung cancer.
- Authors: Gadgeel SM, Wozniak A
- Issue date: 2013 Jul
- Emerging protein kinase inhibitors for non-small cell lung cancer.
- Authors: Liu SV, Subramaniam D, Cyriac GC, Abdul-Khalek FJ, Giaccone G
- Issue date: 2014 Mar
- Lessons learnt from gefitinib and erlotinib: Key insights into small-molecule EGFR-targeted kinase inhibitors in non-small cell lung cancer.
- Authors: Laack E, Sauter G, Bokemeyer C
- Issue date: 2010 Sep