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Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints: Using Public Data to Build Screening Tools within a KNIME Workflow

Steinmetz, FP and Mellor, CL and Meinl, T and Cronin, MTD (2015) Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints: Using Public Data to Build Screening Tools within a KNIME Workflow. MOLECULAR INFORMATICS, 34 (2-3). pp. 171-178. ISSN 1868-1743

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Abstract

Assessing compounds for their pharmacological and toxicological properties is of great importance for industry and regulatory agencies. In this study an approach using open source software and open access databases to build screening tools for receptor-mediated effects is presented. The retinoic acid receptor (RAR), as a pharmacologically and toxicologically relevant target, was chosen for this study. RAR agonists are used in the treatment of a number of dermal conditions and specific types of cancer, such as acute promyelocytic leukemia. However, when administered chronically, there is strong evidence that RAR agonists cause hepatosteatosis and liver injury. After compiling information on ligand-protein-interactions, common substructures and physico-chemical properties of ligands were identified manually and coded into SMARTS strings. Based on these SMARTS strings and calculated physico-chemical features, a rule-based screening workflow was built within the KNIME platform. The workflow was evaluated on two datasets: one with RAR agonists exclusively and another large, chemically diverse dataset containing only a few RAR agonists. Possible modifications and applications of screening workflows, dependent on their purpose, are presented.

Item Type: Article
Additional Information: This is the accepted version of the following article: "Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological Endpoints: Using Public Data to Build Screening Tools within a KNIME Workflow", which has been published in final form at http://dx.doi.org/10.1002/minf.201400188
Uncontrolled Keywords: 0304 Medicinal And Biomolecular Chemistry, 0307 Theoretical And Computational Chemistry, 0601 Biochemistry And Cell Biology
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley-VCH Verlag
Related URLs:
Date Deposited: 02 Mar 2017 16:32
Last Modified: 08 Sep 2017 02:07
DOI or Identification number: 10.1002/minf.201400188
URI: http://researchonline.ljmu.ac.uk/id/eprint/5740

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