Discovery and SAR of novel, potent and selective protein tyrosine phosphatase 1B inhibitors.
A salicylate second site binder was linked to three classes of phosphotyrosine mimetics to produce potent protein tyrosine phosphatase 1B (PTP1B) inhibitors which exhibit significant selectivity against other phosphatases including the most homologous member, TCPTP.
Pei
Zhonghua
Z
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. zhonghua.pei@abbott.com
Li
Xiaofeng
X
Liu
Gang
G
Abad-Zapatero
Cele
C
Lubben
Tom
T
Zhang
Tianyuan
T
Ballaron
Stephen J
SJ
Hutchins
Charles W
CW
Trevillyan
James M
JM
Jirousek
Michael R
MR
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases