Chapter 12 - The Discovery of Lapatinib

Protein kinases are now considered highly druggable due to the fact that there are kinase inhibitors on the market as effective drugs (e.g. Gleevec, Tarceva, and Nexavar). The class of drugs remains plagued by questions about how the inhibition profile affects the efficacy, and whether truly selecti...

Full description

Saved in:
Bibliographic Details
Published inDesigning Multi-Target Drugs pp. 181 - 205
Main Author Lackey, Karen E.
Format Book Chapter
LanguageEnglish
Published The Royal Society of Chemistry 2012
Online AccessGet full text

Cover

More Information
Summary:Protein kinases are now considered highly druggable due to the fact that there are kinase inhibitors on the market as effective drugs (e.g. Gleevec, Tarceva, and Nexavar). The class of drugs remains plagued by questions about how the inhibition profile affects the efficacy, and whether truly selective kinase inhibitors actually exist. Lapatinib remains one of the most selective kinase inhibitors in use for cancer therapy. This chapter will focus on our strategies to discover this novel, dual EGFR and ERBB-2 tyrosine kinase inhibitor using a carefully designed biological evaluation cascade coupled with a multidimensional data analysis. The primary topics discussed will cover the optimization of potency for two kinase targets, yet selective among over 500 kinases within the highly homologous ATP binding site, cellular selectivity and efficacy, and subsequent studies to understand the mechanism of action.
Bibliography:ArticleID:BK9781849733625-00181
ark:/67375/P0J-27BS6MSS-N
istex:626C849F507C1B8C1634EBDCA872E8FD10A85710
ISBN:1849733627
9781849733625
ISSN:2041-3203
2041-3211
DOI:10.1039/9781849734912-00181