Protein-Tyrosine Phosphatase 1B as a Potential Drug Target for Obesity

2003 ◽  
Vol 3 (4) ◽  
pp. 299-304 ◽  
Author(s):  
Shrikrishna Dadke ◽  
Jonathan Chernoff
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Drug Target ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Protein Tyrosine

scholarly journals Toward selective inactivation of protein tyrosine phosphatase 1B via exo-affinity labeling agents

2014 ◽  
Author(s):  
◽  
Andrea Hicks Cummings
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Type Ii Diabetes ◽  
Drug Target ◽  
Tyrosine Phosphatase ◽  
Affinity Labeling ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Signaling ◽  
Protein Targets ◽  
Protein Tyrosine ◽  
Obesity And Cancer

Exo-affinity labeling agents are compounds that achieve selectivity by modifying non-catalytic residues in a protein. They have been utilized as tools in molecular biology and to make successful drugs for protein targets. Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target for type II diabetes, obesity and cancer. However, no compounds have been FDA approved for PTP1B due to selectivity and bioavailability issues with traditional compounds. We propose that exo-affinity labeling agents can be used to achieve selectivity in PTP1B. In this work we have designed, synthesized, and characterized the first exo-affinity for PTP1B. Using this work we can design better exo-affinity labeling agents that can be selective for PTP1B. This may have implications on drug design and general knowledge of protein signaling pathways.

Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

2018 ◽  
Vol 17 (3) ◽  
pp. 134-139
Author(s):  
R.M. Perez-Gutierrez
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Spectroscopic Data ◽  
Methanol Extract ◽  
Tyrosine Phosphatase ◽  
Positive Control ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ic50 Value ◽  
Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

Inhibitor Binding Sites in the Protein Tyrosine Phosphatase SHP-2

2020 ◽  
Vol 20 (11) ◽  
pp. 1017-1030
Author(s):  
Haonan Zhang ◽  
Zhengquan Gao ◽  
Chunxiao Meng ◽  
Xiangqian Li ◽  
Dayong Shi
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Binding Sites ◽  
Drug Target ◽  
Tyrosine Phosphatase ◽  
Cancer Drug ◽  
Cellular Activity ◽  
Binding Modes ◽  
Inhibitor Binding ◽  
Protein Tyrosine

Protein tyrosine phosphatase 2 (SHP-2) has long been proposed as a cancer drug target. Several small-molecule compounds with different mechanisms of SHP-2 inhibition have been reported, but none are commercially available. Pool selectivity over protein tyrosine phosphatase 1 (SHP-1) and a lack of cellular activity have hindered the development of selective SHP-2 inhibitors. In this review, we describe the binding modes of existing inhibitors and SHP-2 binding sites, summarize the characteristics of the sites involved in selectivity, and identify the suitable groups for interaction with the binding sites.

The Involvement of the Mammalian Target of Rapamycin, Protein Tyrosine Phosphatase 1b and Dipeptidase 4 Signaling Pathways in Cancer and Diabetes: A Narrative Review

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiajia Zhang ◽  
Ning Wu ◽  
Dayong Shi
Keyword(s):  
Signaling Pathways ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Mammalian Target Of Rapamycin ◽  
Eukaryotic Cell ◽  
Target Of Rapamycin ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Transduction Mechanisms ◽  
Specific Proteins

Background: The mammalian target of rapamycin (mTOR), protein tyrosine phosphatase 1b (PTP1B) and dipeptidase 4 (DPP4) signaling pathways regulate eukaryotic cell proliferation and metabolism. Previous researches described different transduction mechanisms in the progression of cancer and diabetes. Methodology: We reviewed recent advances in the signal transduction pathways of mTOR, PTP1B and DPP4 regulation and determined the crosstalk and common pathway in diabetes and cancer. Results: We showed that according to numerous past studies, the proteins participate in the signaling networks for both diseases. Conclusion: There are common pathways and specific proteins involved in diabetes and cancer. This article demonstrates and explains the potential mechanisms of association and future prospects for targeting these proteins in pharmacological studies.

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