Welcome to the website of the Computational Toxicology Group. Here we publish the results of our research, offer free access to the toxicological databases and on-line toxicity prediction algorithms developed by the Group members.
Website is divided into two parts - open and accessible for registered users. To log in please create an account choosing Register new account link on your left hand side. Once the account is created we are starting the opening procedure which can take maximum few days. After that user has FULL, FREE access to the whole tox-portal.net content.
CardiacPBPK available online
CardiacPBPK - a tool for the prediction and visualization of time-concentration profiles of drugs in heart tissue in now available online. The application is freely available at https://github.com/jszlek/CardiacPBPK and https://sourceforge.net/projects/cardiacpbpk/. A detailed description of the application can be found in:
Tylutki Z, Szlęk J, Polak S. CardiacPBPK: A tool for the prediction and visualization of time-concentration profiles of drugs in heart tissue. Computers in Biology and Medicine, 2019, 115, 103484; doi:https://doi.org/10.1016/j.compbiomed.2019.103484.
New Toxportal coming soon!
The existing comprehensive database has been upgraded and updated. Several dozens of new records were added. Supplementary information on IC50 values i.e. SEM values, as well as Hill coefficient values with SEM, was provided.
The ion channels inhibition database was extended by three new datasets to provide additional information on TQT study results, reported cases of TdP and effects of DDI on QT interval.
The new portal will be launched in the near future!
Review on the use of mechanistic models in DDD
The review on how quantitative systems pharmacology (QSP), quantitative systems toxicology (QST) and physiologically based pharmacokinetis (PBPK) are used in Model-Informed Drug Discovery and Development was published in:
Polak S, Tylutki Z, Holbrook M, Wiśniowska B. Better prediction of the local concentration–effect relationship: the role of physiologically based pharmacokinetics and quantitative systems pharmacology and toxicology in the evolution of model-informed drug discovery and development. Drug Discovery Today, 2019, 24:1344-1354; doi:https://doi.org/10.1016/j.drudis.2019.05.016.
The cardiac risk algorithm to support the assessment anti-TB agents published in J Pharmacokinet Pharmacodyn.
The empirical decision tree based classifier developed to predict the risk of Torsade de Pointes in now available in:
Polak S, Romero K, Berg A, Patel N, Jamei M, Hermann D, Hanna D. Quantitative approach for cardiac risk assessment and interpretation in tuberculosis drug development.. Journal of Pharmacokinetics and Pharmacodynamics, 2018, doi:10.1007/s10928-018-9580-2.
The proposed cardiac risk algorithm is suitable to support the assessement of novel and repurposed compounds for the treatment of tuberculosis.
A 2-year project in collaboration with BfR
We have just started a two-year project in cooperation with
The German Federal Institute for Risk Assessment (BfR). The project entitled Modeling of dermal absorption of chemicals from solid matrices with integration into PBPK modeling will be carried out in years 2018 - 2019.
Mechanistic PBPK model of the heart published in J Pharm Sci
The mechanistic physiologically based pharmacokinetic (PBPK) model of the heart accounting for inter-individual variability, which we developed recently has been published online. The model's description and the open model R code are available in:
Tylutki Z, Mendyk A, Polak S. Mechanistic PBPK model of the heart accounting for inter-individual variability - development and performance verification. Journal of Pharmaceutical Sciences, 2017, In press, accepted manuscript.
Drug interaction at hERG channel
A new publication from our lab on DDI at the level of the hERG channel available online:
Wisniowska B, Lisowski B, Kulig M, Polak S. Drug interaction at hERG channel: In vitro assessment of the electrophysiological consequences of drug combinations and comparison against theoretical models. Journal of Applied Toxicology, 2017, Accepted for publication.
Workshop & Summer School 2014
6th Workshop on using Computational Methods in Pharmaceutical Sciences is a one day long meeting which will take place on 1st of July, 2014. Workshop will be followed by the Summer School where theoretical considerations will be transferred into the practice with use of the real life case studies.
The main goal of the Workshop is to provide in depth, practical information about design, development, validation and implementation of the computational methods used in the pharmaceutical sciences with focus put on the effective data utilization.
More details and registration at the cpw.edu.pl.
Symposium on Cardiac Safety Simulator
It is our pleasure to announce that the 5th Computational Pharmacy Workshop will take form of the one and half day long Symposium on Cardiac Safety Simulator which will be organized by Simcyp Ltd. (part of Certara) in Sheffield, UK. Symposium starts on the 19th of September (lectures) and continues on the 20th of September with a hands-on part.
For more details and registration please navigate to the Simcyp webpage.
tox-database.net major upgrade
Database containing the drug triggered, in vitro measured cardiac currents inhibition data has been upgraded! Repository contains literature derived values expressed as IC50 for four various currents (IKr, IKs, ICaL, INa), 543 molecules described in more than 1000 records (IKr current: 1137, IKs current: 165, INa current: 177, ICa current: 182).
Please navigate to tox-database.net to access the data.
Conference presentationDr Sebastian Polak will be presenting during the 8th Annual International Conference on Predictive Human Toxicity and ADME/Tox Studies January 24th - 25th, 2013 Brussels, Belgium. Presentation title - In Vitro to Human In Vivo Translation – Proarrhythmic Potency of Dofetilide.
New freely available database!
Another member of the 'tox-' family after the tox-portal.net and tox-comp.net goes live! Please navigate to tox-database.net, login using your tox-portal.net credentials and browse freely all of our databases containing information describing not only IKr (hERG), but also other human cardiomyocyte specific ionic channels inhibition data (IKs, INa, ICa). The database has been described in our latest, just accepted, freely available publication:
Polak S, Wisniowska B, Glinka A, Polak M. tox-database.net - data describing the chemicals triggered in vitro cardiac ionic channels inhibition. BMC Pharmacology and Toxicology, Accepted for publication.
Computational Methods in Pharmaceutical Sciences Workshop
4th Workshop on using Computational Methods in Pharmaceutical Sciences is a one day long training which will take place on 8th of September, 2012. Workshop will be a part of the Computers in Cardiology - CinC 2012 Conference.
The main goal of the Workshop is to provide in depth, practical information about design, development, validation and implementation of the computational methods used in the pharmaceutical sciences with focus put on the early drugs cardiotoxicity prediction.
More details and free registration at the cpw.edu.pl.
Future presentation of the team achievements!11th World Pharma Congress is a one day long training which will take place in Philadelphia, PA (5-7 of June, 2012). On Monday 4th of June pre-conference short course on computational tools for predicting drugs toxicity will cover Dr Sebastian Polak presentation "In vitro-in vivo Extrapolation of the Cardiotoxic Effect: Inter-Individual Variability Matters!".
CPW 2011 workshop materials become available
Lectures and materials presented during the 3rd International Workshop - Computational Pharmacy on-line workshop has been published and are now available for public and download.
Berlin workshop materials become available
Materials presented and cases discussed during the 3rd Predicitive Toxicology meeting in Berlin are now available to download.
Major dataset upgrade
hERG channel inhibition potential database has been upgraded! Files (either .xlsx or .ods) are freely available in the tox-portal.net Repository - after registration. Largest publicly available set of data with triggered by drugs hERG inhibition information contains values expressed as IC50 for 263 molecules described in 642 records.
We will be presenting our results during the following conferences:
Mini-symposium Computational toxicology and pharmacology - in silico drug activity and safety assessment (Saturday, July 2, 11:00) during the 8-th European Conference on Mathematical and Theoretical Biology and Annual Meeting of The Society for Mathematical Biology; June 28 - July 2 2011; Krakow, Poland
MAJOR SYSTEM UPGRADE
New Year brings news to the Tox-Portal.net system. Under the Software link you will find free, system independent system designed for the hERG channel inhibition potential assessment. Extended hERG channel inhibition potential database is freely available in the tox-portal.net Repository - after registration. Files (either .xlsx or .ods) contain data gathered from available literature sources.
Supplementary materials for the conference presentation
hERG channel inhibition potential dataset used for the ANN based model development is now freely available in the tox-portal.net Repository - after registration. Files (either .xlsx or .ods) contain ready-to-use dataset.
Results will be presented during the 14th Online World Conference on Soft Computing in Industrial Applications (WSC14) - http://wsc14.science-city.org
New data files in the Repository
hERG channel inhibition potential database is now freely available in the tox-portal.net Repository - after registration. Files (either .xlsx or .ods) containing data gathered from available literature sources.
2nd International Workshop - Computational Methods in Pharmaceutical Sciences will be organized in year 2010 in Gdansk, Poland as a part of the XXI Scientific Conference of the Polish Pharmaceutical Society. More detailes and registration form can be found at the official website (www.cpw.edu.pl). Stay updated - visit our webpages regularly!