Abstract
As indicated in the previous chapter, molecular therapeutic approaches to cancer are often geared at interfering with signaling pathways that govern cell fate or proliferation. These strategies target kinases, the quintessential signal transducers in the cell. This approach remains challenging because kinases are evolutionarily and therefore structurally related and thus kinase inhibitors often lack specificity or possess uncontrolled cross-reactivities, which may lead to toxic side effects. This chapter illustrates the power of the wrapping concept in developing safer kinase inhibitors, thus unraveling a rational approach to fulfill this therapeutic imperative. The focus of this chapter is the redesign of the anticancer drug imatinib (Gleevec) used to treat chronic myeloid leukemia, where its primary target is the chimeric Bcr-Abl kinase, as well as certain solid tumors based on its impact on the C-Kit kinase.
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Fernandez, A. (2010). Re-engineering an Anticancer Drug to Make It Safer: Modifying Imatinib to Curb Its Side Effects. In: Transformative Concepts for Drug Design: Target Wrapping. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-11792-3_8
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DOI: https://doi.org/10.1007/978-3-642-11792-3_8
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