Discovery of potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70

…, SG Pradeepan, C Bartlett, RS Bohacek…

Index: Vu, Chi B.; Corpuz, Evelyn G.; Merry, Taylor J.; Pradeepan, Selvaluxmi G.; Bartlett, Catherine; Bohacek, Regine S.; Botfield, Martyn C.; Eyermann, Charles J.; Lynch, Berkley A.; MacNeil, Ian A.; Ram, Mary K.; Van Schravendijk, Marie Rose; Violette, Shelia; Sawyer, Tomi K. Journal of Medicinal Chemistry, 1999 , vol. 42, # 20 p. 4088 - 4098

Full Text: HTML

Citation Number: 101

Abstract

A series of 1, 2, 4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200-400-fold more potent than the native, monophosphorylated tetrapeptide sequences. When compared with the high-affinity ζ-1- ITAM peptide (Ac-NQL-pYNELNLGRREE-pYDVLD-NH2, wherein pY refers to ...