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Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach

Xiangyu Zhang, Hailun Jiang, Wei Li, Jian Wang, Maosheng Cheng
2017 Computational and Mathematical Methods in Medicine  
In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors.  ...  Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes.  ...  To our knowledge, this is the first time that systematical combinations of ligandbased and structure-based approaches provide an insight into PTP1B's active site and the interaction with its ligands by  ... 
doi:10.1155/2017/4245613 pmid:29441120 pmcid:PMC5758944 fatcat:dg3e6bh5w5ew5okdjzjroiplgi

Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B

Guevara-Garcia
2010 Drug Design, Development and Therapy  
Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B).  ...  In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during  ...  (SYBYL, MOE); to Prof Dr Reiner Lammers, for in vitro inhibition and activity tests; to PhD Dr Nicolas Lembert, for the extra-pancreatic tests; to Prof Dr H.P.T.  ... 
doi:10.2147/dddt.s8445 fatcat:vvr2jlmenjgejfuquv4kssotje

Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B

Thomas Scior, José Antonio Guevara-García, F J Melendez, Hassan H Abdallah, Quoc-Tuan Do, Philippe Bernard
2010 Drug Design, Development and Therapy  
Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B).  ...  In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during  ...  (SYBYL, MOE); to Prof Dr Reiner Lammers, for in vitro inhibition and activity tests; to PhD Dr Nicolas Lembert, for the extra-pancreatic tests; to Prof Dr H.P.T.  ... 
pmid:20957214 pmcid:PMC2948933 fatcat:quna3v4hsfgw7nzmqonspcla2a

Inhibition of Yersinia Tyrosine Phosphatase by Furanyl Salicylate Compounds

L. Tautz, S. Bruckner, S. Sareth, A. Alonso, J. Bogetz, N. Bottini, M. Pellecchia, T. Mustelin
2004 Journal of Biological Chemistry  
We used a novel and cost-effective approach, in which leads from a chemical library screening were analyzed and computationally docked into the crystal structure of YopH.  ...  To avoid detection and targeting by the immune system, the plague-causing bacterium Yersinia pestis uses a type III secretion system to deliver a set of inhibitory proteins into the cytoplasm of immune  ...  DISCUSSION In this study we use an approach to inhibitor design, which can be characterized as a hybrid between traditional high throughput screening and rational design based on the structure of the  ... 
doi:10.1074/jbc.m413122200 pmid:15615724 fatcat:dnj4bus5avbr3pa32jj3yc7vne

Toward a Molecular Understanding of the Interaction of Dual Specificity Phosphatases with Substrates: Insights from Structure-Based Modeling and High Throughput Screening

Ahmet Bakan, John Lazo, Peter Wipf, Kay Brummond, Ivet Bahar
2008 Current Medicinal Chemistry  
These studies emphasize the utility of developing computational models and methods that meet the two major challenges currently faced in structure-based in silico design of lead compounds: the conformational  ...  Recent experimental and virtual HTS studies, as well as advances in molecular modeling, provide new insights into the potential mechanisms for substrate recognition and binding by this important class  ...  Fig. (2) illustrates the catalytic domain of a DSP, cell division cycle 25B (Cdc25B) phosphatase, in comparison to two extensively studied cell signaling enzymes, protein tyrosine phosphatase 1B (PTP1B  ... 
doi:10.2174/092986708785909003 pmid:18855677 pmcid:PMC2764859 fatcat:pnq7p7p26vgdvmdvtnkpq6clem

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions

Harikrishna Reddy R, Hackyoung Kim, Seungbin Cha, Bongsoo Lee, Young Jun Kim
2017 Journal of Microbiology and Biotechnology  
Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions.  ...  Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis,  ...  An illustrative structure of protein tyrosine phosphatase 1B (PTP1B). Fig. 3 . 3 Fig. 3.  ... 
doi:10.4014/jmb.1701.01079 pmid:28238001 fatcat:kxtgoy3kh5dnpksn6dudket4sy

Computer Simulation of TSP1 Inhibition of VEGF–Akt–eNOS: An Angiogenesis Triple Threat

Hojjat Bazzazi, Yu Zhang, Mohammad Jafarnejad, Jeffrey S. Isenberg, Brian H. Annex, Aleksander S. Popel
2018 Frontiers in Physiology  
The matricellular protein thrombospondin-1 (TSP1) is a potent inhibitor of angiogenesis.  ...  The model further predicts that combination strategy involving depletion of CD47 and inhibition of TSP1 binding to CD47 is necessary for effective recovery of signaling to eNOS.  ...  VEGFR2 has a ligand-binding site (L), a tyrosine phosphorylation site (represented as Y1175), and a ligand independent coupling site (c).  ... 
doi:10.3389/fphys.2018.00644 pmid:29899706 pmcid:PMC5988849 fatcat:s6am5nnekjhnnjnmkpvr23r5ba

Cell signaling regulation by protein phosphorylation: a multivariate, heterogeneous, and context-dependent process

Evan K Day, Nisha G Sosale, Matthew J Lazzara
2016 Current Opinion in Biotechnology  
The study of signaling regulation by protein phosphorylation is complicated in part by the sheer scope of the kinome and phosphoproteome, dependence of signaling protein functionality on cellular localization  ...  In one example, ligand binding to the extracellular domain of a receptor initiates a network of intracellular biochemical reactions that affect cell phenotypes by modifying gene expression, metabolism,  ...  A recent study described a new multiplexed method with absolute quantification and large dynamic range of protein phosphorylation and applied the method to quantify the effects of EGFR inhibition in glioblastoma  ... 
doi:10.1016/j.copbio.2016.06.005 pmid:27393828 pmcid:PMC4975652 fatcat:xoxs7enrxraizbekanko6oqxdq

Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala

S. R. McLean
2005 Molecular Cancer Therapeutics  
These results highlight some of the structural and functional consequences of the Val 654 Ala mutation in relapsing imatinib-resistant GIST and emphasize the importance of tumor genetics in drug development  ...  Several activating mutations in the cKIT receptor tyrosine kinase are associated with the development and progression of gastrointestinal stromal tumors (GIST).  ...  Acknowledgments We thank the patients involved in this study and Drs. D. Lagos and S. Henderson for helpful revision of the article.  ... 
doi:10.1158/1535-7163.mct-05-0070 pmid:16373716 fatcat:snnd7kx4lfdstgxfpdgygua7wa

Structure-based development of target-specific compound libraries

Andrew J.W. Orry, Ruben A. Abagyan, Claudio N. Cavasotto
2006 Drug Discovery Today  
A structure-based target-specific library can save time and money by reducing the number of compounds to be experimentally tested, also improving the drug discovery success rate by identifying more-potent  ...  Currently, there is a trend towards the construction of receptorstructure-based focused libraries.  ...  Acknowledgements The authors thank Hugo O. Villar, from Altoris, for comments and insightful discussions.  ... 
doi:10.1016/s1359-6446(05)03717-7 pmid:16580603 fatcat:i6o7xom5lbbrrkfr5zxmiwys44

Methods of probing the interactions between small molecules and disordered proteins

Gabriella T. Heller, Francesco A. Aprile, Michele Vendruscolo
2017 Cellular and Molecular Life Sciences (CMLS)  
interactions between disordered proteins; (2) those that inhibit the aberrant aggregation of disordered proteins, and (3) those that lead to binding disordered proteins in their monomeric states.  ...  A major bottleneck for the identification of compounds capable of interacting with these proteins and modulating their disease-promoting behaviour is the development of effective techniques to probe such  ...  Low resolution Variable Protein-tyrosine phosphatase 1B and trodusquemine [56] [114, 115] Thermal denaturation screening Detection of monomeric binders Non-quantitative High Nuclear protein  ... 
doi:10.1007/s00018-017-2563-4 pmid:28631009 pmcid:PMC5533867 fatcat:z52be5hh3jb5zoqvsz5ahdy7iy

Structural insights into mode of actions of novel natural Mycobacterium protein tyrosine phosphatase B inhibitors

Jaspreet Kaur Dhanjal, Sonam Grover, Sudhanshu Sharma, Ajeet Singh, Abhinav Grover
2014 BMC Genomics  
The present study aims at indentifying potent inhibitors of mPTPB by using computational approaches of ligand based molecular modeling and docking studies.  ...  Mycobacterium tuberculosis secretes a virulence factor, protein tyrosine phosphatase B (mPTPB) in the cytoplasm of host macrophage which suppresses its natural innate immune response and helps the pathogen  ...  Acknowledgements AG is thankful to Jawaharlal Nehru University for usage of all computational facilities. AG is grateful to Department of Science and Technology, Government of India.  ... 
doi:10.1186/1471-2164-15-s1-s3 pmid:24564493 pmcid:PMC4046716 fatcat:ecf6fryoxjgdbd6kztgbnfmeke

NSC114792, a novel small molecule identified through structure-based computational database screening, selectively inhibits JAK3

Byung-Hak Kim, Jun-Goo Jee, Chang-Hong Yin, Claudio Sandoval, Somasundaram Jayabose, Daisuke Kitamura, Erika A Bach, Gyeong-Hun Baeg
2010 Molecular Cancer  
To identify novel small molecule inhibitors of JAK3, we performed structure-based virtual screen using the 3D structure of JAK3 kinase domain and the NCI diversity set of compounds.  ...  Human or animals lacking either JAK3 or the common gamma chain (γc) expression display severe combined immunodeficiency disease, indicating the crucial role of JAK3 in T-cell development and the homeostasis  ...  Schultz from the NCI Developmental Therapeutics Program for providing the compound of NSC114792. This work was supported by the Children's Cancer Fund (Millwood, NY).  ... 
doi:10.1186/1476-4598-9-36 pmid:20149240 pmcid:PMC2830973 fatcat:uycwynnoknhnzmmvpum7fa63xi

The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma

E. M. Van Allen, N. Wagle, A. Sucker, D. J. Treacy, C. M. Johannessen, E. M. Goetz, C. S. Place, A. Taylor-Weiner, S. Whittaker, G. V. Kryukov, E. Hodis, M. Rosenberg (+20 others)
2013 Cancer Discovery  
The spectrum of clinical genetic resistance mechanisms to RAF inhibitors and options for salvage therapy are incompletely understood.  ...  Besides previously characterized alterations, we discovered a "long tail" of new mitogen-activated protein kinase (MAPK) pathway alterations (MAP2K2, MITF) that confer RAF inhibitor resistance.  ...  Authors' Contributions Acknowledgments The authors thank the patients who were enrolled in this study. Grant Support  ... 
doi:10.1158/2159-8290.cd-13-0617 pmid:24265153 pmcid:PMC3947264 fatcat:esv6wt24ubhzrecwp23uwl7nzm

SHP2 Inhibition Influences Therapeutic Response to Tepotinib in Tumors with MET Alterations

Linda Pudelko, Frank Jaehrling, Christof Reusch, Sanziago Vitri, Christopher Stroh, Nina Linde, Michael P. Sanderson, Doreen Musch, Catherine Jorand Lebrun, Marina Keil, Christina Esdar, Andree Blaukat (+3 others)
2020 iScience  
Alternative signaling pathways potentially diminish the effect of tepotinib monotherapy, and the combination of tepotinib with an SHP2 inhibitor enables the control of tumor growth in cells with MET genetic  ...  An Src homology 2 domain-containing phosphatase 2 (SHP2) inhibitor delayed the emergence of tepotinib resistance and synergized with tepotinib in treatment-naive and tepotinib-resistant cells as well as  ...  Structural and molecular insight into resistance mechanisms of first generation cMET inhibitors. ACS Med. Chem. Lett. 10, 1322-1327.  ... 
doi:10.1016/j.isci.2020.101832 pmid:33305187 pmcid:PMC7718487 fatcat:f6up2wzcrfgcbcabluli5gkjza
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