Abstract
Since protein kinases are frequently mutated or otherwise deregulated in human malignancies, they serve as a target for differentiating between tumor cells and normal tissues. Imatinib mesylat (IM), an inhibitor of the BCR-ABL tyrosine kinase was introduced in 2001 and has revolutionized the treatment of patients with chronic myeloid leukemia (CML). Since 2005 a second generation of tyrosine kinase inhibitors is to follow in Imatinibs footsteps: The development of these new small molecules was promoted by the identification of potential target kinases within the cellular signaling apparatus. Modern biochemical tools provide relevant amounts of these target kinases necessary for high throughput screening (HTS) campaigns and for elucidation of their 3-D structure by crystallography. Supported by computational chemistry the resulting data have enabled rational drug design. In this review low molecular weight inhibitors used for the CML treatment are summarized, pointing out their chemical similarities and differences.
Keywords: CML, Imatinib, aurora kinase, BCR-ABL, SGX393, tyrosine kinase inhibitor
Current Pharmaceutical Design
Title: Imatinib and Its Successors – How Modern Chemistry has Changed Drug Development
Volume: 15 Issue: 2
Author(s): Bernhard A. Muller
Affiliation:
Keywords: CML, Imatinib, aurora kinase, BCR-ABL, SGX393, tyrosine kinase inhibitor
Abstract: Since protein kinases are frequently mutated or otherwise deregulated in human malignancies, they serve as a target for differentiating between tumor cells and normal tissues. Imatinib mesylat (IM), an inhibitor of the BCR-ABL tyrosine kinase was introduced in 2001 and has revolutionized the treatment of patients with chronic myeloid leukemia (CML). Since 2005 a second generation of tyrosine kinase inhibitors is to follow in Imatinibs footsteps: The development of these new small molecules was promoted by the identification of potential target kinases within the cellular signaling apparatus. Modern biochemical tools provide relevant amounts of these target kinases necessary for high throughput screening (HTS) campaigns and for elucidation of their 3-D structure by crystallography. Supported by computational chemistry the resulting data have enabled rational drug design. In this review low molecular weight inhibitors used for the CML treatment are summarized, pointing out their chemical similarities and differences.
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Cite this article as:
Muller A. Bernhard, Imatinib and Its Successors – How Modern Chemistry has Changed Drug Development, Current Pharmaceutical Design 2009; 15 (2) . https://dx.doi.org/10.2174/138161209787002933
DOI https://dx.doi.org/10.2174/138161209787002933 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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