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.

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

Inhibitors of Protein Tyrosine Phosphatase 1B from Marine Natural Products

2017 ◽  
Vol 14 (7) ◽  
pp. e1600462 ◽  
Author(s):  
Yue Zhou ◽  
Weirui Zhang ◽  
Xiaoyu Liu ◽  
Haobing Yu ◽  
Xiaoling Lu ◽  
...  
Keyword(s):  
Natural Products ◽  
Protein Tyrosine Phosphatase ◽  
Marine Natural Products ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine

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.

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

scholarly journals Biomolecular Interactions of Small-molecule Inhibitors Affecting the YopH Protein Tyrosine Phosphatase

2013 ◽  
Vol 81 (3) ◽  
pp. 323-333 ◽  
Author(s):  
Megan Hogan ◽  
Medhanit Bahta ◽  
Scott Cherry ◽  
George T. Lountos ◽  
Joseph E. Tropea ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Small Molecule Inhibitors ◽  
Tyrosine Phosphatase ◽  
Biomolecular Interactions ◽  
Protein Tyrosine

Abstract A83: Profiling potent, novel protein tyrosine phosphatase 4A3 small molecule inhibitors for ovarian cancer.

2016 ◽  
Author(s):  
Elizabeth R. Sharlow ◽  
Joseph M. Salamoun ◽  
Kelley E. McQueeney ◽  
Sophie Lewandowski ◽  
Jennifer Bryant ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Small Molecule ◽  
Protein Tyrosine Phosphatase ◽  
Small Molecule Inhibitors ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine ◽  
Novel Protein
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