New assignments for multitasking signal transduction inhibitors.
An article presented in this issue of Molecular Pharmacology (p. 1527) provides an intriguing example of how tyrosine kinase inhibitors can be put to many uses. In this article, the action of dasatinib (BMS-354825) is contrasted with that of imatinib, a kinase inhibitor that is currently being used to treat chronic myelogenous leukemia and other disorders. Both pharmacologic inhibitors target several tyrosine kinases, including Bcr-Abl and the platelet-derived growth factor receptor (PDGFR). Up to this point, the PDGFR has not been a primary therapeutic target for this class of agents. The work of Chen and colleagues shows that dasatinib is a particularly potent inhibitor of PDGFR and that the compound also targets Src kinase. The authors suggest that this combination of activities could be useful in the treatment of vascular obstructive diseases. Although a lack of absolute specificity has typically been regarded as a pharmacologic drawback, this study exemplifies how drugs with multiple molecular targets can potentially provide a very beneficial spectrum of therapeutic activities in multiple disease states.
Department of Pharmaceutical Sciences, P.O. Box 646534, Washington State University, Pullman, WA 99164-6534, USA.
Zhihong
Z
Zhang
Kathryn E
KE
Meier
D000818:Animals; D001549:Benzamides; D002460:Cell Line; D000069439:Dasatinib; D000068877:Imatinib Mesylate; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology*
D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D000069439:Dasatinib