• 제목/요약/키워드: PTP1B

검색결과 85건 처리시간 0.018초

Effects of PTP1B Inhibitors and Taurine on Blood Lipid Profiles in Adolescents Obesity Model Rats

  • Cheong, Sun-Hee;Hyeongjin Cho;Chang, Kyung-Ja
    • 대한지역사회영양학회:학술대회논문집
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    • 대한지역사회영양학회 2004년도 춘계학술대회
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    • pp.437.1-437
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    • 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)

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Docking Study of Biflavonoids, Allosteric Inhibitors of Protein Tyrosine Phosphatase 1B

  • Lee, Jee-Young;Jung, Ki-Woong;Woo, Eun-Rhan;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • 제29권8호
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    • pp.1479-1484
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    • 2008
  • Protein tyrosine phosphatase (PTP) 1B is the superfamily of PTPs and a negative regulator of multiple receptor tyrosine kinases (RTKs). Inhibition of protein tyrosine phosphatase 1B (PTP1B) has been proposed as a strategy for the treatment of type 2 diabetes and obesity. Recently, it has been reported that amentoflavone, a biflavonoid extracted from Selaginella tamariscina, inhibited PTP1B. In the present study, docking model between amentoflavone and PTP1B was determined using automated docking study. Based on this docking model and the interactions between the known inhibitors and PTP1B, we determined multiple pharmacophore maps which consisted of five features, two hydrogen bonding acceptors, two hydrogen bonding donors, and one lipophilic. Using receptor-oriented pharmacophore-based in silico screening, we searched the biflavonoid database including 40 naturally occurring biflavonoids. From these results, it can be proposed that two biflavonoids, sumaflavone and tetrahydroamentoflavone can be potent allosteric inhibitors, and the linkage at 5',8''-position of two flavones and a hydroxyl group at 4'-position are the critical factors for their allosteric inhibition. This study will be helpful to understand the mechanism of allosteric inhibition of PTP1B by biflavonoids and give insights to develop potent inhibitors of PTP1B.

Screening of Marine Microbial Extracts for Tyrosine Phosphatase 1B Inhibitors

  • Sohn, Jae-Hak;Park, Sun Jung;Seo, Changon;Chun, Bokyung;Oh, Hyuncheol
    • 한국해양바이오학회지
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    • 제2권4호
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    • pp.230-233
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    • 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 $30{\mu}g/mL$.

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PTP1B Inhibitory Secondary Metabolites from Marine-Derived Fungal Strains Penicillium spp. and Eurotium sp.

  • Sohn, Jae Hak;Lee, Yu-Ri;Lee, Dong-Sung;Kim, Youn-Chul;Oh, Hyuncheol
    • Journal of Microbiology and Biotechnology
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    • 제23권9호
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    • pp.1206-1211
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    • 2013
  • The selective inhibition of PTP1B has been widely recognized as a potential drug target for the treatment of type 2 diabetes and obesity. In the course of screening for PTP1B inhibitory fungal metabolites, the organic extracts of several fungal species isolated from marine environments were found to exhibit significant inhibitory effects, and the bioassay-guided investigation of these extracts resulted in the isolation of fructigenine A (1), cyclopenol (2), echinulin (3), flavoglaucin (4), and viridicatol (5). The structures of these compounds were determined mainly by analysis of NMR and MS data. These compounds inhibited PTP1B activity with 50% inhibitory concentration values of 10.7, 30.0, 29.4, 13.4, and 64.0 ${\mu}M$, respectively. Furthermore, the kinetic analysis of PTP1B inhibition by compounds 1 and 5 suggested that compound 1 inhibited PTP1B activity in a noncompetitive manner, whereas compound 5 inhibited PTP1B activity in a competitive manner.

생약의 Protein Tyrosine Phosphatase 1B (PTP1B) 저해활성 검색 (Screening of the Inhibitory Activity of Medicinal Plants against Protein Tyrosine Phosphatase 1B)

  • 홍정현;이명선;배은영;김영호;오현철;오원근;김보연;안종석
    • 생약학회지
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    • 제35권1호통권136호
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    • pp.16-21
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    • 2004
  • Protein tyrosine phosphatase 1B(PTP1B) is thought to be a negative regulator in insulin signal-transduction pathway. Insulin-resistance by the activation of PTP1B is a hallmark of both type 2 diabetes and obesity. Thus, the compounds inhibiting PTP1B can improve insulin resistance and can be effective in treating type 2 diabetes and obesity. The methanol extracts of 160 herbal medicines were screened for the inhibitory activity against PTP1B. Among the tested extracts, methanol extracts of Amsonia elliptica, Areca catechu, Benincasa hispida, Morus alba, Salvia miltiorrhiza, Siegesbeckia orientalis, and Trichosanthes kirilowii showed relatively strong inhibitory activity against PTP1B.

생약의 Protein Tyrosine Phosphatase 1B 저해활성 검색 (Screening of Medicinal Herbs for Inhibitory Activity against Protein Tyrosine Phosphatase 1B)

  • 이우정;김수남;윤구
    • 생약학회지
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    • 제41권3호
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    • pp.227-231
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    • 2010
  • Protein tyrosine phosphatase 1B (PTP1B) is predicted to be therapeutic target in treatment of type 2 diabetes and obesity. Thus, in order to search for PTP1B inhibitors, we screened the inhibitory activity of PTP1B in the water extracts of 84 medicinal herbs. Among them, the extracts of Pini Folium, Magnoliae Cortex, Artemisiae asiaticae Herba, Schizonepetae Herba, Menthae Herba, Mume Fructus, Cimicifugae Rhizoma, and Amomi Cardamomi Fructus showed relatively significant (58-68%) inhibitory activity against PTP1B. Especially, the methylene chloride fraction of the methanol extract of Menthae Herba (81% inhibition at 30 ${\mu}g$/ml) showed more potent inhibitory activity against PTP1B than others.

어성초로부터 분리된 Quercetin의 Protein Tyrosine Phosphatase 1B 활성 (Protein Tyrosine Phosphatase 1B Activity of Quercetin from Houttuynia Cordata)

  • 최화정;배은영;노용주;백승화
    • 동의생리병리학회지
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    • 제22권6호
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    • pp.1532-1536
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    • 2008
  • Quercetin which isolated form the roots of Houttuynia cordata. was determined on the basis of IR, ID and 2D NMR specta by direct comparison with authentic compounds. Protein tyrosine phophatase 1B (PTP1B) is thought to be a negative regulator in insulin signal-transduction pathway. Insulin-resistance by the activation of PTP1B is a hallmark of both type 2 diabetes and obesity. Thus, the compound inhibiting PTP1B can improve insulin resistance and can be effective in treating type 2 diabetes and obesity. Quercetin which measured the inhibitory activity against PTP1B was 92.1% inhibition in the 30 ${\mu}g$/mL, 83.4% inhibition in the 6 ${\mu}g$/mL and 76.5% inhibition in the 3 ${\mu}g$/mL. These results suggest that quercetin retains a potential PTP1B activity.

Neuroprotective Effects of Protein Tyrosine Phosphatase 1B Inhibition against ER Stress-Induced Toxicity

  • Jeon, Yu-Mi;Lee, Shinrye;Kim, Seyeon;Kwon, Younghwi;Kim, Kiyoung;Chung, Chang Geon;Lee, Seongsoo;Lee, Sung Bae;Kim, Hyung-Jun
    • Molecules and Cells
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    • 제40권4호
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    • pp.280-290
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    • 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.

The Molecular Modeling of Novel Inhibitors of Protein Tyrosine Phosphatase 1B Based on Catechol by MD and MM-GB (PB)/SA Calculations

  • Kocakaya, Safak Ozhan
    • Bulletin of the Korean Chemical Society
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    • 제35권6호
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    • pp.1769-1776
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    • 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.

Molecular Docking Study of Anti-diabetic Xanthones from Garcinia Xanthochymus

  • Babu, Sathya
    • 통합자연과학논문집
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    • 제10권3호
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    • pp.137-140
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    • 2017
  • Diabetes mellitus has become a major growing public health problem worldwide. More than 90% of all diabetes cases are classified as type 2 diabetes (T2D), which is also known as non-insulin dependent diabetes. Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin signal transduction pathway and has emerged as novel therapeutic strategy for the treatment of type 2 diabetes. PTP1B inhibitors enhance the sensibility of insulin receptor (IR) and have favorable curing effect for insulin resistance-related diseases. Recently twelve anti-diabetic xanthones were isolated from the bark of Garcinia xanthochymus. Hence, in the present study, molecular docking was carried out for these twelve xanthones. The objective of this work is to study the interaction of the newly isolated xanthones with PTP1B. The docking results showed that xanthones have good interactions and has better docking score with PTP1B and suggest LYS120 and ASP181 are the important residues involved in interaction between PTP1B enzyme and the xanthones.