Serotonin derivatives as a new class of non-ATP-competitive receptor tyrosine kinase inhibitors.
The discovery of new templates and their subsequent elaboration to clinically useful receptor tyrosine kinase (RTK) inhibitors continues to be an important issue. RTKs are a class of enzymes responsible for the activation of different cellular signal transduction cascades. The majority of the known small molecules RTK inhibitors are ATP-competitive and they are multiple targeted inhibitors. We describe here serotonin derivatives as a new class of multiple targeted RTK inhibitors. In contrast to most other RTK inhibitors they act via a non-ATP-competitive (allosteric) mechanism. Furthermore, they are able to inhibit the proliferation of HUVE cells, fibroblasts and two cancer cell lines.
Büttner
Anita
A
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany.
Cottin
Thomas
T
Xu
Jing
J
Tzagkaroulaki
Lito
L
Giannis
Athanassios
A
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000494:pharmacology; D000494:Allosteric Regulation; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D047428:Protein Kinase Inhibitors; D012701:Serotonin; D000255:Adenosine Triphosphate; D020794:Receptor Protein-Tyrosine Kinases