• Journal of Marine Bioscience and Biotechnology
• /
• v.2 no.4
• /
• pp.230-233
• /
• 2007

Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin signaling, and selective inhibition of PTP1B has served as a potential drug target for the treatment of type 2 diabetes. As part of our searching for PTP1B inhibitors from natural products, the extracts of marine microorganisms were screened for the inhibitory effects on the activity of protein tyrosine phosphatase 1B (PTP1B). Among the tested 304 extracts, 29 extracts exhibited inhibition rate ranging 40.1 - 83.6 % against PTP1B at the concentration level of $30{\mu}g/mL$.

• Proceedings of the KSCN Conference
• /
• 2004.05a
• /
• pp.437.1-437
• /
• 2004

The protein, called PTP1B (protein tyrosine phosphatase 1B), joins a list of enzymes that mice are associated with obesity. The purpose of this study was to investigate the effects of PTP1B inhibitors and taurine on blood lipid profiles in adolescents obesity model rats. Three week-old thirty-six male Sprague-Dawley rats were randomly assigned to six groups (high fat diet group; HFD group, high fat diet ＋ taurine group; HF＋TR group, high fat diet＋PTP1B inhibitor A group; HF＋A group, high fat diet＋PTP1B inhibitor B; HF＋B group, high fat diet＋PTP1B inhibitor A＋taurine group; HF＋A＋TR group, high fat diet ＋ PTP1B inhibitor B＋taurine group; HF＋B＋TR group).(omitted)

• Bulletin of the Korean Chemical Society
• /
• v.33 no.1
• /
• pp.275-277
• /
• 2012

• Bulletin of the Korean Chemical Society
• /
• v.25 no.9
• /
• pp.1303-1304
• /
• 2004

• Bulletin of the Korean Chemical Society
• /
• v.32 no.1
• /
• pp.31-32
• /
• 2011

• Bulletin of the Korean Chemical Society
• /
• v.35 no.6
• /
• pp.1769-1776
• /
• 2014

Binding modes of a series of catechol derivatives such as protein tyrosine phosphatase 1B (PTP1B) inhibitors were identified by molecular modeling techniques. Docking, molecular dynamics simulations and free energy calculations were employed to determine the modes of these new inhibitors. Binding free energies were calculated by involving different energy components using the Molecular Mechanics-Poisson-Boltzmann Surface Area and Generalized Born Surface Area methods. Relatively larger binding energies were obtained for the catechol derivatives compared to one of the PTP1B inhibitors already in use. The Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) free energy decomposition analysis indicated that the hydroxyl functional groups and biphenyl ring system had favorable interactions with Met258, Tyr46, Gln262 and Phe182 residues of PTP1B. The results of hydrogen bound analysis indicated that catechol derivatives, in addition to hydrogen bonding interactions, Val49, Ile219, Gln266, Asp181 and amino acid residues of PTP1B are responsible for governing the inhibitor potency of the compounds. The information generated from the present study should be useful for the design of more potent PTP1B inhibitors as anti-diabetic agents.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.5
• /
• pp.1505-1508
• /
• 2012

Protein tyrosine phosphatase 1B (PTP1B) is a key factor in negative regulation of the insulin pathway, and is a promising target for the treatment of type-II diabetes, obesity and cancer. Herein, compound ($\mathbf{4}$) was first observed to have moderate inhibitory activity against PTP1B with an $IC_{50}$ value of $13.72{\pm}1.53{\mu}M$. To obtain more potent PTP1B inhibitors, we synthesized a series of chalcone derivatives using compound ($\mathbf{4}$) as the lead compound. Compound $\mathbf{4l}$ ($IC_{50}=3.12{\pm}0.18{\mu}M$) was 4.4-fold more potent than the lead compound $\mathbf{4}$ ($IC_{50}=13.72{\pm}1.53{\mu}M$), and more potent than the positive control, ursolic acid ($IC_{50}=3.40{\pm}0.21{\mu}M$). These results may help to provide suitable drug-like lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

• Molecules and Cells
• /
• v.40 no.4
• /
• pp.280-290
• /
• 2017

Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers ($eIF2{\alpha}$ phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.10
• /
• pp.2861-2862
• /
• 2013

• Bulletin of the Korean Chemical Society
• /
• v.34 no.8
• /
• pp.2487-2490
• /
• 2013

SA51, a medium potency inhibitor of protein tyrosine phosphatase 1B (PTP1B), was identified to be a potent inhibitor of $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$). Consistent with this, SA51 prevented lipopolysaccharide (LPS)-induced breakdown of $I{\kappa}B{\alpha}$ in macrophages. The effects of SA51 in mice were compared with those of structurally related compounds, SA18 and SA32, which were previously reported as inhibitors of both enzymes - less potent against $IKK{\beta}$ but more potent against PTP1B compared to SA51. SA51 improved glucose tolerance and lipid parameters in mice, consistent with the results reported for $IKK{\beta}^{+/-}$ mice. In contrast, SA18 and SA32 showed anti-obesity effects without anti-diabetic effects. Collectively, the effects of SA51 could be due largely to the inhibition of $IKK{\beta}$, whereas SA18 and SA32 may be more likely to inhibit PTP1B, consistent with their relative in vitro inhibitory effects.