Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide.
The active metabolite of leflunomide, A77 1726 inhibits the proliferation of a variety of mammalian cell lines in culture. Epidermal growth factor (EGF)-dependent proliferation is inhibited by A77 1726 at an effective dose of 30-40 microM. A77 1726 appears to directly inhibit the EGF receptor tyrosine-specific kinase activity both in intact cells and purified EGF receptors at the same effective dose. These data suggest that leflunomide inhibits cellular proliferation by the inhibition of tyrosine-specific kinase activities.
Mattar
T
T
Department of Immunology, Johannes Gutenberg University, Mainz, Germany.
Kochhar
K
K
Bartlett
R
R
Bremer
E G
EG
Finnegan
A
A
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002478:Cells, Cultured; D003437:Crotonates; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005347:Fibroblasts; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D007624:KB Cells; D000077339:Leflunomide; D008297:Male; D009570:Nitriles; D010766:Phosphorylation; D012867:Skin / Q000378:metabolism; D014052:Toluidines; D014407:Tumor Cells, Cultured
D000814:Aniline Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003437:Crotonates; D006885:Hydroxybutyrates; D007555:Isoxazoles; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D066246:ErbB Receptors; D000077339:Leflunomide