Discovery of a novel submicromolar inhibitor of the lymphoid specific tyrosine phosphatase.
We report here a class of thiazolidine-2,4-diones and 2-thioxothiazolidin-4-ones as potent inhibitors of the lymphoid specific tyrosine phosphatase (Lyp) identified from high throughput screens. Chemical modification by incorporating the known phosphotyrosine (pTyr) mimics led to the discovery of a salicylate-based inhibitor with submicromolar potency.
Xie
Yuli
Y
Department of Medicine, Columbia University, 650 W 168th Street, BB 1029, New York, NY 10032, USA.
Liu
Yidong
Y
Gong
Gangli
G
Rinderspacher
Alison
A
Deng
Shi-Xian
SX
Smith
Deborah H
DH
Toebben
Udo
U
Tzilianos
Effie
E
Branden
Lars
L
Vidović
Dusica
D
Chung
Caty
C
Schürer
Stephan
S
Tautz
Lutz
L
Landry
Donald W
DW
D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008956:Models, Chemical; D018716:Molecular Mimicry; D019000:Phosphotyrosine / Q000737:chemistry; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000037:antagonists & inhibitors*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000494:pharmacology*; D053778:Thiazolidines / Q000138:chemical synthesis / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; D053778:Thiazolidines; D019000:Phosphotyrosine; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases