Small Molecule Peptidomimetics Containing a Novel Phosphotyrosine Bioisostere Inhibit Protein Tyrosine Phosphatase 1B and Augment Insulin Action‡

Biochemistry ◽  
2001 ◽  
Vol 40 (19) ◽  
pp. 5642-5654 ◽  
Author(s):  
John E. Bleasdale ◽  
Derek Ogg ◽  
Barbara J. Palazuk ◽  
Cynthia S. Jacob ◽  
Michael L. Swanson ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Insulin Action ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

Structure-Based Discovery of Small Molecule Inhibitors Targeted to Protein Tyrosine Phosphatase 1B

2000 ◽  
Vol 43 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Mauro Sarmiento ◽  
Li Wu ◽  
Yen-Fang Keng ◽  
Li Song ◽  
Zhaowen Luo ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Small Molecule Inhibitors ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

scholarly journals PAIN-less identification and evaluation of small molecule inhibitors against protein tyrosine phosphatase 1B

MedChemComm ◽  
2017 ◽  
Vol 8 (6) ◽  
pp. 1220-1224 ◽  
Author(s):  
Hamid R. Nasiri ◽  
Philipp Mracek ◽  
Steffen K. Grimm ◽  
Janine Gastaldello ◽  
Adrian Kolodzik ◽  
...  
Keyword(s):  
Natural Products ◽  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Small Molecule Inhibitors ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Set Up ◽  
Assay Interference

A miniaturized assay was set up to test a set of natural products against protein tyrosine phosphatase 1B (PTP1B). By using several read-out and counter assays, berberine and palmatine were identified as PAINS (pan-assay interference compounds) and α-TOS as a novel inhibitor of PTP1B.

scholarly journals Developmental Switch from Prolonged Insulin Action to Increased Insulin Sensitivity in Protein Tyrosine Phosphatase 1B-Deficient Hepatocytes

Endocrinology ◽  
2007 ◽  
Vol 148 (2) ◽  
pp. 594-608 ◽  
Author(s):  
Agueda Gonzalez-Rodriguez ◽  
Jill E. Clampit ◽  
Oscar Escribano ◽  
Manuel Benito ◽  
Cristina M. Rondinone ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Protein Tyrosine Phosphatase ◽  
Insulin Action ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Developmental Switch

scholarly journals Correlation Between Nasal Epithelial Injury and In Vitro Cytotoxicity Using a Series of Small Molecule Protein Tyrosine Phosphatase 1B Inhibitors Investigated for Reversal of Leptin Resistance in Obesity

2017 ◽  
Vol 36 (4) ◽  
pp. 303-313
Author(s):  
Alan P. Brown ◽  
Chandrassegar Saravanan ◽  
Patrick Devine ◽  
Maria Magnifico ◽  
Jiaping Gao ◽  
...  
Keyword(s):  
Food Consumption ◽  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Sodium Dodecylbenzene Sulfonate ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Nasal Injury ◽  
Ptp1b Inhibitors

This research provides a cautionary example when evaluating changes in behavioral end points with respect to postulated pharmacologic activity. Various small molecule substrate mimetic protein tyrosine phosphatase 1B (PTP1B) inhibitors were investigated as pharmacologic agents for decreasing food consumption using intranasal (IN) dosing as a means for direct nose-to-brain delivery along the olfactory/trigeminal nerve pathways. Although food consumption was decreased in diet-induced obese (DIO) mice, nasal discharge was observed. Studies were conducted to investigate local effects on the nasal airway and to develop structure–activity relationships. Intranasal administration of PTP1B inhibitors at ≥0.03 mg/d to DIO mice produced dose-dependent injury to various cell types of the nasal epithelia. Protein tyrosine phosphatase 1B inhibitors with calculated log octanol >3.0 were the most toxic. Whereas a pharmacologically inactive analog of a PTP1B inhibitor produced nasal injury, along with decreased food consumption, the marketed IN drug ketorolac produced no lesions at the same dose of 0.3 mg/d and only minor changes at 3 mg/d. Rat skin fibroblast cells were exposed in vitro to PTP1B inhibitors, ketorolac, paraquat, and the detergent sodium dodecylbenzene sulfonate (NDS) followed by measures of cytotoxicity. The most potent PTP1B inhibitors were similar to NDS, whereas ketorolac was the least toxic compound. Cytotoxic potency in vitro was similar to in vivo. In conclusion, PTP1B inhibitors injured nasal epithelium through a mechanism independent of PTP1B inhibition and likely due to nonspecific cytotoxicity such as disruption of the cell membrane. Decreased food consumption in DIO mice was due to toxicity rather than a pharmacologic mode of action.

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.

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