Tyrphostins: tyrosine kinase blockers as novel antiproliferative agents and dissectors of signal transduction.
Protein tyrosine kinases (PTKs) are members of a growing family of oncoproteins and protooncoproteins that play a pivotal role in normal and abnormal proliferative processes. This hallmark identifies these unique proteins as potential targets for antiproliferative therapy. This review discusses the current status of PTK inhibitors, with special emphasis on tyrphostins as antiproliferative agents and as potential drugs for cancers, leukemias, psoriasis, and restenosis as well as other proliferative conditions. The development of tyrphostins as selective signal blockers can be viewed as a first step toward the development of "smart" cocktails as antiproliferative agents. Each of these custom-made cocktails will be aimed at proliferative conditions whose transduction pathways can be characterized by molecular tools. The review also discusses the use of PTK blockers as tools to study signal transduction processes in which protein tyrosine kinases are implicated.
Levitzki
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Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Israel.
D000818:Animals; D001597:Benzylidene Compounds / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006131:Growth Inhibitors; D006801:Humans; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D001597:Benzylidene Compounds; D006131:Growth Inhibitors; D009570:Nitriles; D011505:Protein-Tyrosine Kinases