CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds
In vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1689 |
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| author | Alexey A. Lagunin Anastasia V. Rudik Pavel V. Pogodin Polina I. Savosina Olga A. Tarasova Alexander V. Dmitriev Sergey M. Ivanov Nadezhda Y. Biziukova Dmitry S. Druzhilovskiy Dmitry A. Filimonov Vladimir V. Poroikov |
| author_facet | Alexey A. Lagunin Anastasia V. Rudik Pavel V. Pogodin Polina I. Savosina Olga A. Tarasova Alexander V. Dmitriev Sergey M. Ivanov Nadezhda Y. Biziukova Dmitry S. Druzhilovskiy Dmitry A. Filimonov Vladimir V. Poroikov |
| author_sort | Alexey A. Lagunin |
| collection | DOAJ |
| description | In vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs of drug development and the assessment of new pharmaceutical agent perspectives. In 2018, we developed the first freely available web application (CLC-Pred) for the qualitative prediction of cytotoxicity against 278 tumor and 27 normal cell lines based on structural formulas of 59,882 compounds. Here, we present a new version of this web application: CLC-Pred 2.0. It also employs the PASS (Prediction of Activity Spectra for Substance) approach based on substructural atom centric MNA descriptors and a Bayesian algorithm. CLC-Pred 2.0 provides three types of qualitative prediction: (1) cytotoxicity against 391 tumor and 47 normal human cell lines based on ChEMBL and PubChem data (128,545 structures) with a mean accuracy of prediction (AUC), calculated by the leave-one-out (LOO CV) and the 20-fold cross-validation (20F CV) procedures, of 0.925 and 0.923, respectively; (2) cytotoxicity against an NCI60 tumor cell-line panel based on the Developmental Therapeutics Program’s NCI60 data (22,726 structures) with different thresholds of IG<sub>50</sub> data (100, 10 and 1 nM) and a mean accuracy of prediction from 0.870 to 0.945 (LOO CV) and from 0.869 to 0.942 (20F CV), respectively; (3) 2170 molecular mechanisms of actions based on ChEMBL and PubChem data (656,011 structures) with a mean accuracy of prediction 0.979 (LOO CV) and 0.978 (20F CV). Therefore, CLC-Pred 2.0 is a significant extension of the capabilities of the initial web application. |
| first_indexed | 2024-03-09T12:18:03Z |
| format | Article |
| id | doaj.art-8ae13d638cb64fbe9977835aa5ca41c7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:18:03Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8ae13d638cb64fbe9977835aa5ca41c72023-11-30T22:44:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242168910.3390/ijms24021689CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike CompoundsAlexey A. Lagunin0Anastasia V. Rudik1Pavel V. Pogodin2Polina I. Savosina3Olga A. Tarasova4Alexander V. Dmitriev5Sergey M. Ivanov6Nadezhda Y. Biziukova7Dmitry S. Druzhilovskiy8Dmitry A. Filimonov9Vladimir V. Poroikov10Department of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaDepartment of Bioinformatics, Institute of Biomedical Chemistry, 119435 Moscow, RussiaIn vitro cell-line cytotoxicity is widely used in the experimental studies of potential antineoplastic agents and evaluation of safety in drug discovery. In silico estimation of cytotoxicity against hundreds of tumor cell lines and dozens of normal cell lines considerably reduces the time and costs of drug development and the assessment of new pharmaceutical agent perspectives. In 2018, we developed the first freely available web application (CLC-Pred) for the qualitative prediction of cytotoxicity against 278 tumor and 27 normal cell lines based on structural formulas of 59,882 compounds. Here, we present a new version of this web application: CLC-Pred 2.0. It also employs the PASS (Prediction of Activity Spectra for Substance) approach based on substructural atom centric MNA descriptors and a Bayesian algorithm. CLC-Pred 2.0 provides three types of qualitative prediction: (1) cytotoxicity against 391 tumor and 47 normal human cell lines based on ChEMBL and PubChem data (128,545 structures) with a mean accuracy of prediction (AUC), calculated by the leave-one-out (LOO CV) and the 20-fold cross-validation (20F CV) procedures, of 0.925 and 0.923, respectively; (2) cytotoxicity against an NCI60 tumor cell-line panel based on the Developmental Therapeutics Program’s NCI60 data (22,726 structures) with different thresholds of IG<sub>50</sub> data (100, 10 and 1 nM) and a mean accuracy of prediction from 0.870 to 0.945 (LOO CV) and from 0.869 to 0.942 (20F CV), respectively; (3) 2170 molecular mechanisms of actions based on ChEMBL and PubChem data (656,011 structures) with a mean accuracy of prediction 0.979 (LOO CV) and 0.978 (20F CV). Therefore, CLC-Pred 2.0 is a significant extension of the capabilities of the initial web application.https://www.mdpi.com/1422-0067/24/2/1689cytotoxicitycell linesmechanism of actionin silico predictionSARPASS |
| spellingShingle | Alexey A. Lagunin Anastasia V. Rudik Pavel V. Pogodin Polina I. Savosina Olga A. Tarasova Alexander V. Dmitriev Sergey M. Ivanov Nadezhda Y. Biziukova Dmitry S. Druzhilovskiy Dmitry A. Filimonov Vladimir V. Poroikov CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds International Journal of Molecular Sciences cytotoxicity cell lines mechanism of action in silico prediction SAR PASS |
| title | CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds |
| title_full | CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds |
| title_fullStr | CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds |
| title_full_unstemmed | CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds |
| title_short | CLC-Pred 2.0: A Freely Available Web Application for In Silico Prediction of Human Cell Line Cytotoxicity and Molecular Mechanisms of Action for Druglike Compounds |
| title_sort | clc pred 2 0 a freely available web application for in silico prediction of human cell line cytotoxicity and molecular mechanisms of action for druglike compounds |
| topic | cytotoxicity cell lines mechanism of action in silico prediction SAR PASS |
| url | https://www.mdpi.com/1422-0067/24/2/1689 |
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