Small molecule regulation of phosphatase-dependent cell signaling pathways.
Small molecules provide exceptionally useful tools for probing signaling targets relevant for cancer and stem cell differentiation. In contrast to genetic approaches, the application of small molecules generally offers a graded and reversible disruption of a particular pathway. The vast array of theoretical chemical entities that exist in the chemical universe are now becoming available through the production and distribution of chemical libraries generated by both traditional and combinatorial methods, which are suitable for pharmacological use. Convenient and inexpensive cell-free and cell-based assays can be used to identify chemicals that exhibit desirable antisignaling properties. We illustrate a model of how agents targeted against signaling macromolecules involved in cancer, namely dual specificity protein phosphatases, can be identified.
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. lazo@imap.pitt.edu
John S
JS
Lazo
Peter
P
Wipf
D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D015398:Signal Transduction / Q000502:physiology*; D020687:cdc25 Phosphatases / Q000145:classification / Q000187:drug effects*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D020687:cdc25 Phosphatases