Biological activity of tyrosine kinase inhibitors: novel agents for psoriasis therapy.
Uncontrolled signaling from protein tyrosine kinases (PTKs) can lead to numerous proliferative and inflammatory diseases, and identification of the specific PTKs that play a key role in a defined disease could potentially lead to a selective therapeutic agent. In psoriasis, the balance of signals that regulate the homeostasis of normal epidermis is altered. Several lines of evidence suggest a role for the epidermal growth factor receptor (EGFR) system in this process. The PTK inhibitor from the tyrphostins family--AG-1571 (SU-5271) potently inhibits proliferation of psoriatic keratinocytes in excellent correlation with its EGFR kinase inhibitory activity, and was in clinical trials by SUGEN Inc. The recently developed in vivo models of psoriasis may become useful tools to evaluate PTK inhibitors to treat the disease and open a novel specific therapeutic approach. This article summarizes recent progress in the development of PTK inhibitors in the treatment of psoriasis.
Ben-Bassat
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Israel National Skin Bank, Hadassah Medical Organization, Jerusalem. benbassat@md.huji.ac.il
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000201:enzymology*
D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases