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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Synthesis and biological evaluation of aeroplysinin analogues: a new class of receptor tyrosine kinase inhibitors.

Receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR) and the platelet-derived growth factor receptor (PDGFR), are critically involved in the transduction of mitogenic signals across the plasma membrane and therefore in the regulation of cell growth and proliferation. Enhanced RTK activity is associated with proliferative diseases such as cancer, psoriasis and atherosclerosis, while decreased function may be associated for instance with diabetes. EGFR and PDGFR are selectively inhibited by analogues of the marine natural product aeroplysinin. The synthetic inhibitors display IC50 values in the low micromolar range and in contrast to the natural product show pronounced inhibitory activity in cultured cells in vivo. The mechanism of inhibition is likely based on a covalent modification of the target enzymes by reaction of epoxy ketone 8 with various nucleophiles.[1]

References

  1. Synthesis and biological evaluation of aeroplysinin analogues: a new class of receptor tyrosine kinase inhibitors. Hinterding, K., Knebel, A., Herrlich, P., Waldmann, H. Bioorg. Med. Chem. (1998) [Pubmed]
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