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Tumor Liberated Protein (TLP) from lung cancer and perspectives for immunotherapy

Giulio Tarro
2012 Drug Designing: Open Access  
Based on structural analysis of dozens of high resolution crystal structures of p38α inhibitor complexes, PH-797804 is predicted to possess high level of specificity across the broad human kinase genome  ...  We used a structural bioinformatics approach to identify two selectivity elements encoded by the TXXXG sequence motif on p38α kinase hinge.  ...  Based on structural analysis of dozens of high resolution crystal structures of p38α inhibitor complexes, PH-797804 is predicted to possess high level of specificity across the broad human kinase genome  ... 
doi:10.4172/2169-0138.s1.001 fatcat:sd6gpt2j2vgjnn7bgfkgv3bddq

Computational methods for analysis and inference of kinase/inhibitor relationships

Fabrizio Ferrè, Antonio Palmeri, Manuela Helmer-Citterich
2014 Frontiers in Genetics  
molecules, in the in silico prediction of inhibition for those neglected kinases for which no systematic analysis has been carried yet, in the selection of novel inhibitors with desired selectivity, and  ...  However, off-target ligand binding and complex and sometimes unexpected kinase/inhibitor relationships can occur for seemingly unrelated kinases, stressing that computational approaches are needed for  ...  can be used for the in silico prediction of inhibition for those neglected kinases for which no systematic analysis has been carried yet, and for the selection of inhibitors with desired promiscuity.  ... 
doi:10.3389/fgene.2014.00196 pmid:25071826 pmcid:PMC4075008 fatcat:qo57mpdr5veodhkujgl4dqunyu

Computational Modeling of Kinase Inhibitor Selectivity

Govindan Subramanian, Manish Sud
2010 ACS Medicinal Chemistry Letters  
An exhaustive computational exercise on a comprehensive set of 15 therapeutic kinase inhibitors was undertaken to identify as to which compounds hit which kinase off-targets in the human kinome.  ...  Although the kinase selectivity propensity of each inhibitor against ∼480 kinase targets is predicted, we compared our predictions to ∼280 kinase targets for which consistent experimental data are available  ...  the prediction of potential kinase inhibitor selectivity using the kinase cocrystallized inhibitors.  ... 
doi:10.1021/ml1001097 pmid:26677403 pmcid:PMC4669537 fatcat:buwopjndyvehpmkftunony6aba

Combinatorial Clustering of Residue Position Subsets Predicts Inhibitor Affinity across the Human Kinome

Drew H. Bryant, Mark Moll, Paul W. Finn, Lydia E. Kavraki, Mona Singh
2013 PLoS Computational Biology  
However, computational approaches to comparing the 3-dimensional geometry and physicochemical properties of key binding site residue positions have been shown to be informative of inhibitor selectivity  ...  Here, CCORPS is applied to the problem of identifying structural features of the kinase ATP binding site that are informative of inhibitor binding.  ...  Acknowledgments The authors would like to thank the members of the Kavraki group at Rice University, Dr. Yousif Shamoo, and the anonymous reviewers for their valuable comments.  ... 
doi:10.1371/journal.pcbi.1003087 pmid:23754939 pmcid:PMC3675009 fatcat:pf2ajlr5n5fr7fofrujqw7sziq

A structural informatics approach to mine kinase knowledge bases

Natasja Brooijmans, Dominick Mobilio, Gary Walker, Ramaswamy Nilakantan, Rajiah A. Denny, Eric Feyfant, David Diller, Jack Bikker, Christine Humblet
2010 Drug Discovery Today  
We illustrate the systems in the context of the Abelson kinase and related inhibitor structures. Reviews INFORMATICS  ...  In this paper, we describe a combination of structural informatics approaches developed to mine data extracted from existing structure knowledge bases (Protein Data Bank and the GVK database) with a focus  ...  John at GVK Bio for their participation in the development of the structural informatics systems described in this manuscript.  ... 
doi:10.1016/j.drudis.2009.11.005 pmid:19948242 fatcat:uqoiewvn5vdo3bb5icj5a34kly

In silico Methods for Design of Kinase Inhibitors as Anticancer Drugs

Zarko Gagic, Dusan Ruzic, Nemanja Djokovic, Teodora Djikic, Katarina Nikolic
2020 Frontiers in Chemistry  
In this review, computational methods used in rational drug design of kinase inhibitors are discussed and compared, considering some representative case studies.  ...  Kinase inhibitors are clinically very important and widely used antineoplastic drugs.  ...  ACKNOWLEDGMENTS The authors kindly acknowledge national project number 172033 supported by the Ministry of Education, Science and Technological development of the Republic of Serbia.  ... 
doi:10.3389/fchem.2019.00873 pmid:31970149 pmcid:PMC6960140 fatcat:725g6v22hfhgniplq2xdlxed4m

Re-positioning of known drugs for Pim-1 kinase target using molecular docking analysis

Housna Arrouchi, Biotechnology Laboratory (Medbiotech), BioInova Research center, Rabat Medical and Pharmacy School, Mohammed V University in Rabat, Rabat, Morroco, Wiame Lakhlili, Azeddine Ibrahimi
2019 Bioinformation  
Therefore, it is of interest to re-profile known drugs against the Pim-1 kinase target using molecular docking analysis.  ...  Results show that known drugs such as nilotinib, vemurafenib, Idelalisib, and other small kinases inhibitors have high binding ability with Pim-1 kinase for consideration as potential inhibitors.  ...  This work was also supported, by a grant from Institute of Cancer Research of the foundation Lalla Salma.  ... 
doi:10.6026/97320630015116 pmid:31435157 pmcid:PMC6677905 fatcat:pvhlpqaisjdgpptb3zhqx7wlxu

Cross-Reactivity Virtual Profiling of the Human Kinome by X-ReactKIN: A Chemical Systems Biology Approach

Michal Brylinski, Jeffrey Skolnick
2010 Molecular Pharmaceutics  
In particular, the development of highly selective kinase inhibitors is complicated by the strong conservation of the ATP-binding site across the kinase family.  ...  Furthermore, in a case study, we demonstrate how X-React KIN can support the development of selective inhibitors by optimizing the selection of kinase targets for small-scale counter-screen experiments  ...  This work was supported in part by Grants GM-48835 and GM-37408 of the Division of General Medical Sciences of the National Institutes of Health.  ... 
doi:10.1021/mp1002976 pmid:20958088 pmcid:PMC2997910 fatcat:3mnpocfakjflnody3nuwlk63bq

Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

Bryce K. Allen, Saurabh Mehta, Stewart W. J. Ember, Ernst Schonbrunn, Nagi Ayad, Stephan C. Schürer
2015 Scientific Reports  
Our method integrated machine learning using big datasets of kinase inhibitors and structure-based drug design.  ...  We developed a general computational screening approach to identify novel dual kinase/bromodomain inhibitors from millions of commercially available small molecules.  ...  Signatures (LINCS) Program (http://www.lincsproject.org/) and the trans-NIH Big Data to Knowledge (BD2K) initiative (http://www.bd2k.nih.gov).  ... 
doi:10.1038/srep16924 pmid:26596901 pmcid:PMC4657038 fatcat:guqen5jzdjdg5hgkwwtwgosvl4

Structure–kinetic relationships that control the residence time of drug–target complexes: insights from molecular structure and dynamics

Hao Lu, James N Iuliano, Peter J Tonge
2018 Current Opinion in Chemical Biology  
However, while the optimization of thermodynamic affinity through approaches such as structure-based drug design is now relatively straight forward, less is understood about the molecular interactions  ...  Time-dependent target occupancy is a function of both the thermodynamics and kinetics of drugtarget interactions.  ...  JNI was supported by the National Institutes of Health GM092714 and a Graduate Assistance in Areas of National Need (GAANN) Fellowship.  ... 
doi:10.1016/j.cbpa.2018.06.002 pmid:29986213 pmcid:PMC6066427 fatcat:kfs5tpwur5bqliu645da6jp7fy

The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design

Giorgio Cozza
2017 Pharmaceuticals  
of CK2 inhibitors.  ...  supported by crystallographic analysis.  ...  Conflicts of Interest: The author declares no conflict of interest.  ... 
doi:10.3390/ph10010026 pmid:28230762 pmcid:PMC5374430 fatcat:krlqf3bjozbezocfkkwtdbiif4

Kinase selectivity potential for inhibitors targeting the ATP binding site: a network analysis

Danzhi Huang, Ting Zhou, Karine Lafleur, Cristina Nevado, Amedeo Caflisch
2009 Computer applications in the biosciences : CABIOS  
The multiple-structure alignment is then used to encode the known strategies for developing selective inhibitors into a fingerprint.  ...  Finally, a network analysis is used to partition the kinases into clusters according to similarity of their fingerprints, i.e., physico-chemical characteristics of the residues responsible for selective  ...  We thank Dr Stefan Knapp for providing a list of unique kinase PDB structures.  ... 
doi:10.1093/bioinformatics/btp650 pmid:19942586 fatcat:tc5dey7cgbh4rbwcat6gi2wm7m

Structure-guided selection of specificity determining positions in the human Kinome

Mark Moll, Paul W. Finn, Lydia E. Kavraki
2016 BMC Genomics  
It is well-known that inhibitors of protein kinases bind with very different selectivity profiles. This is also the case for inhibitors of many other protein families.  ...  We have developed a structural bioinformatics approach which provides an analysis of key determinants of binding selectivity as a tool to enhance the rational design of drugs with a specific selectivity  ...  Declarations This article has been published as part of BMC Genomics Vol 17 Suppl 4 2016: Selected articles from the IEEE International Conference on Bioinformatics and Biomedicine 2015: genomics.  ... 
doi:10.1186/s12864-016-2790-3 pmid:27556159 pmcid:PMC5001202 fatcat:sau7qmkoozhnnl75yhe2zw4pda

Structure-guided selection of Specificity Determining Positions in the human kinome

Mark Moll, Paul W. Finn, Lydia E. Kavraki
2015 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)  
It is well-known that inhibitors of protein kinases bind with very different selectivity profiles. This is also the case for inhibitors of many other protein families.  ...  We have developed a structural bioinformatics approach which provides an analysis of key determinants of binding selectivity as a tool to enhance the rational design of drugs with a specific selectivity  ...  Declarations This article has been published as part of BMC Genomics Vol 17 Suppl 4 2016: Selected articles from the IEEE International Conference on Bioinformatics and Biomedicine 2015: genomics.  ... 
doi:10.1109/bibm.2015.7359650 dblp:conf/bibm/MollFK15 fatcat:fnazoa5li5gfbnofg5mn2jfqei

High quality, small molecule-activity datasets for kinase research

Rajan Sharma, Stephan C. Schürer, Steven M. Muskal
2016 F1000Research  
The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR) data.  ...  Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease.  ...  Kinase inhibitor datasets The wealth of kinase inhibitor data presents opportunities for analysis as a whole or by integrating such data into various computational platforms to support development and  ... 
doi:10.12688/f1000research.8950.1 pmid:27429748 pmcid:PMC4943296 fatcat:jffqbord7vaxre5rz7yorg7r7y
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