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Crowdsourced mapping of unexplored target space of kinase inhibitors

Anna Cichońska, Balaguru Ravikumar, Robert J. Allaway, Fangping Wan, Sungjoon Park, Olexandr Isayev, Shuya Li, Michael Mason, Andrew Lamb, Ziaurrehman Tanoli, Minji Jeon, Sunkyu Kim (+95 others)
2021 Nature Communications  
Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data.  ...  AbstractDespite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged.  ...  Acknowledgements The authors thank the IDG Kinase Data and Resource Generation Center for generating new sets of target activity data for the Challenge Rounds 1 and 2, Olle Hansson (FIMM) for technical  ... 
doi:10.1038/s41467-021-23165-1 pmid:34083538 fatcat:otj4dir66bhahci4fj56ifbw5a

Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD

Roberto Pagliarini, Christine Podrini
2021 Frontiers in Medicine  
The integration of computational data analysis that accompanies experimental findings was pivotal in the identification of metabolic reprogramming in ADPKD.  ...  In ADPKD, a broad range of dysregulated pathways have been found.  ...  However, the development of reliable tools to integrate different datasets remains a challenge due to low data comparability and consistency.  ... 
doi:10.3389/fmed.2021.740087 pmid:34901057 pmcid:PMC8652061 fatcat:pz3mlcmu2fhldk3twn2yd4nf4m

Polypharmacology modelling using proteochemometrics (PCM): recent methodological developments, applications to target families, and future prospects

Isidro Cortés-Ciriano, Qurrat Ul Ain, Vigneshwari Subramanian, Eelke B. Lenselink, Oscar Méndez-Lucio, Adriaan P. IJzerman, Gerd Wohlfahrt, Peteris Prusis, Thérèse E. Malliavin, Gerard J. P. van Westen, Andreas Bender
2015 MedChemComm  
Proteochemometric (PCM) modelling is a computational method to model the bioactivity of multiple ligands against multiple related protein targets simultaneously.  ...  Introduction 1.1 Available bioactivity data is growing: but can we make sense of it?  ...  on a large scale to an output variable of interest.  ... 
doi:10.1039/c4md00216d fatcat:kvf2cuib6fbjta4dferweweugm

Protein domain-based prediction of drug/compound–target interactions and experimental validation on LIM kinases

Tunca Doğan, Ece Akhan Güzelcan, Marcus Baumann, Altay Koyas, Heval Atas, Ian R. Baxendale, Maria Martin, Rengul Cetin-Atalay, Feixiong Cheng
2021 PLoS Computational Biology  
DRUIDom is experimentally validated by syntheses and bioactivity analyses of compounds predicted to target LIM-kinase proteins, which play critical roles in the regulation of cell motility, cell cycle  ...  Next, a million-scale dataset of small molecule compounds, including those mapped to domains in the previous step, are clustered based on their molecular similarities, and their domain associations are  ...  of using large-scale experimental bioactivity data accumulated in public databases such as Pub-Chem and ChEMBL.  ... 
doi:10.1371/journal.pcbi.1009171 pmid:34843456 pmcid:PMC8659301 fatcat:5yvxwtolfrejhl2v5r4nvzif6u

Crowdsourced mapping of unexplored target space of kinase inhibitors [article]

Anna Cichonska, Balaguru Ravikumar, Robert J Allaway, Sungjoon Park, Fangping Wan, Olexandr Isayev, Shuya Li, Michael J Mason, Andrew Lamb, Zia-ur-Rehman Tanoli, Minji Jeon, Sunkyu Kim (+16 others)
2020 bioRxiv   pre-print
A total of 268 ML predictions were scored in unpublished bioactivity data sets.  ...  The open-source ML algorithms together with the novel dose-response data for 905 bioactivities between 95 compounds and 295 kinases provide a unique resource for extending the druggable kinome.  ...  Acknowledgements The authors thank the IDG Kinase Data and Resource Generation Center for generating new sets of target activity data for the Challenge Rounds  ... 
doi:10.1101/2019.12.31.891812 fatcat:qnkxwa3jnbh7nabv7qetyfwmsa

In silico target fishing: Predicting biological targets from chemical structure

Jeremy L. Jenkins, Andreas Bender, John W. Davies
2006 Drug Discovery Today : Technologies  
Combines a large number of bioactivity and screening databases ChemBank A public, web-based service from the Broad Institute's Chemical Biology Program.  ...  We provide a comparative review of recent studies in which data mining, similarity, or docking of chemical structures is used to elucidate target class or mechanism of action.  ...  NIBR and Paul Clemons (the Broad Institute) and Brian Schoichet (UCSF) for helpful discussions on in silico target fishing.  ... 
doi:10.1016/j.ddtec.2006.12.008 fatcat:7p6uljq43balfmxczca7eb7joi

Comparison of Deep Learning With Multiple Machine Learning Methods and Metrics Using Diverse Drug Discovery Data Sets

Alexandru Korotcov, Valery Tkachenko, Daniel P. Russo, Sean Ekins
2017 Molecular Pharmaceutics  
These data sets represent whole cell screens, individual proteins, physicochemical properties as well as a data set with a complex end point.  ...  In this study, we have used data sets for solubility, probe-likeness, hERG, KCNQ1, bubonic plague, Chagas, tuberculosis, and malaria to compare different machine learning methods using FCFP6 fingerprints  ...  AUC, F1-score and other metrics listed in data analysis section were computed using those probabilities.  ... 
doi:10.1021/acs.molpharmaceut.7b00578 pmid:29096442 pmcid:PMC5741413 fatcat:cd6rwu46ljh5nkiloyiw6hpx5q

Identification of drug candidates and repurposing opportunities through compound–target interaction networks

Anna Cichonska, Juho Rousu, Tero Aittokallio
2015 Expert Opinion on Drug Discovery  
Janica Wakkinen and Dr. Simon Anders for many useful discussions about different types of experimental assays and computational models.  ...  Tang J, Szwajda A, Shakyawar S. Making sense of large-scale kinase inhibitor bioactivity data sets: A comparative and integrative analysis.  ...  The network concept allows one to abstract, integrate, and organize the data from large-scale experiments, facilitating the extraction of useful information from complex biological systems.  ... 
doi:10.1517/17460441.2015.1096926 pmid:26429153 fatcat:vtz37pji6jcnlmcuw6k3v7t3kq

Will the chemical probes please stand up?

Ctibor Škuta, Christopher Southan, Petr Bartůněk
2021 RSC Medicinal Chemistry  
This study provides a comprehensive and comparative overview of probe sources, structures and targets.  ...  The analysis encompasses 4466 chemical probe candidates supported by evidence of specific binding to 796 human proteins.  ...  Acknowledgements This work was supported by the MEYS grant LM2018130 and by RVO: 68378050-KAV-NPUI. Useful comments from the two referees and discussions with Prof.  ... 
doi:10.1039/d1md00138h fatcat:kolwpchrrfh3vamcm5pldoxa4u

Combined Virtual and Experimental Screening for CK1 Inhibitors Identifies a Modulator of p53 and Reveals Important Aspects of in Silico Screening Performance

Vassilios Myrianthopoulos, Olivier Lozach, Danae Zareifi, Leonidas Alexopoulos, Laurent Meijer, Vassilis Gorgoulis, Emmanuel Mikros
2017 International Journal of Molecular Sciences  
A compound collection of pronounced structural diversity was comprehensively screened for inhibitors of the DNA damage-related kinase CK1. The collection was evaluated in vitro.  ...  A potent and selective CK1 inhibitor was discovered and its capacity to modulate the endogenous levels of the CK1-regulated tumor suppressor p53 was demonstrated in cancer cell lines.  ...  In this study, an extensive set of ATP-competitive kinase inhibitors previously published [38] by our group was used with kinase GSK-3β, and an optimal factor of 0.8 was determined for protein VdW scaling  ... 
doi:10.3390/ijms18102102 pmid:28984824 pmcid:PMC5666784 fatcat:zej4dmp3wzft5ldsfcc6k6kwgi

Self-Organized Evolutionary Process in Sets of Interdependent Variables near the Midpoint of Phase Transition in K-Satisfiability [chapter]

Michael Korkin
2001 Lecture Notes in Computer Science  
Ackerman, John T Strategic Studies Quarterly: An Air Force-Sponsored Strategic Forum for Military, Government, and Academic Professionals. Volume 2, Number 1 -7 Acuff, Hugh F  ...  ; analysis of remote sensing data and imagery; development of remote sensing products; photogrammetry; and aerial photography.  ...  On the other hand, computer main memory is relatively limited and constrained compared to the amount of data in a large collection.  ... 
doi:10.1007/3-540-45443-8_20 fatcat:ght26tu6avh57kkp54kifofaee

A Multilayer Network Approach for Guiding Drug Repositioning in Neglected Diseases

Ariel José Berenstein, María Paula Magariños, Ariel Chernomoretz, Fernán Agüero, Timothy G. Geary
2016 PLoS Neglected Tropical Diseases  
We modeled genomic (proteins) and chemical (bioactive compounds) data as a multilayer weighted network graph that takes advantage of bioactivity data across 221 species, chemical similarities between 1.7  ...  In this work we took advantage of data from extensively studied organisms like human, mouse, E. coli and yeast, among others, to develop a novel integrative network model to prioritize and identify candidate  ...  Morten Nielsen (Universidad de San Martín-CONICET, Argentina; and Center for Biological Sequence Analysis, Technical University of Denmark,  ... 
doi:10.1371/journal.pntd.0004300 pmid:26735851 pmcid:PMC4703370 fatcat:fifuctne3bfkvjwagz57b3xgb4

Computational approaches in target identification and drug discovery

Theodora Katsila, Georgios A. Spyroulias, George P. Patrinos, Minos-Timotheos Matsoukas
2016 Computational and Structural Biotechnology Journal  
Such methods are depicted and discussed, with the aim to provide a general view of computational tools and databases available.  ...  No doubt, data volume and diversity have dramatically increased by the advent of new technologies and open data initiatives.  ...  The authors have no conflict of interests to disclose.  ... 
doi:10.1016/j.csbj.2016.04.004 pmid:27293534 pmcid:PMC4887558 fatcat:b4wmdd25qrg55lhwacydf4auuu

Targeting Kinases in Fasciola hepatica: Anthelminthic Effects and Tissue Distribution of Selected Kinase Inhibitors

Carolin M. Morawietz, Hicham Houhou, Oliver Puckelwaldt, Laura Hehr, Domenic Dreisbach, Annika Mokosch, Elke Roeb, Martin Roderfeld, Bernhard Spengler, Simone Haeberlein
2020 Frontiers in Veterinary Science  
: the Abelson tyrosine kinase (ABL-TK) inhibitor imatinib and the polo-like 1 (PLK1) inhibitor BI2536.  ...  Together with a significantly higher transcriptional expression of PLK1 in adult compared to immature worms, this argues for a role of PLK1 in fluke reproduction.  ...  We previously identified potential orthologs of ABL-TK and PLK1 kinases in F. hepatica (18) , which makes imatinib and BI2536 excellent candidates for a pilot study of kinase inhibitors with fasciolicidal  ... 
doi:10.3389/fvets.2020.611270 pmid:33409299 pmcid:PMC7779637 fatcat:br5whttdmjdz5pmbw5qavyl2yy

A high content, small molecule screen identifies candidate molecular pathways that regulate rod photoreceptor outer segment renewal

Leah J. Campbell, Megan C. West, Abbie M. Jensen
2018 Scientific Reports  
The data generated by this screen provides a foundation for further investigation of the signaling pathways that regulate photoreceptor outer segment renewal.  ...  Therefore, a better understanding of the cellular maintenance of the photoreceptor outer segment may provide guidance for the design and optimization of treatments to prevent vision loss and restore or  ...  We also thank Anna Liu, PhD (Department of Mathematics and Statistics, University of Massachusetts Amherst) for guidance on statistical analysis.  ... 
doi:10.1038/s41598-018-32336-y pmid:30228302 pmcid:PMC6143611 fatcat:mnocxy4wunh7bgluweu27jw3na
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