Abstract:
:Protein tyrosine phosphatase 1B (PTP1B) as a key negative regulator of both insulin and leptin receptor pathways has been an attractive therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. With the goal of enhancing potency and selectivity of the PTP1B inhibitors, a series of methyl salicylate derivatives as ABC type PTP1B inhibitors (P1-P7) were discovered. More importantly, compound P6 exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP). Further studies on cellular activities revealed that compound P6 could enhance insulin-mediated insulin receptor β (IRβ) phosphorylation and insulin-stimulated glucose uptake.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Liu P,Du Y,Song L,Shen J,Li Qdoi
10.1016/j.ejmech.2016.04.014subject
Has Abstractpub_date
2016-08-08 00:00:00pages
27-33eissn
0223-5234issn
1768-3254pii
S0223-5234(16)30296-3journal_volume
118pub_type
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