Systematic analysis of the potential off-target activities of osimertinib by computational target fishing
Autor: | Shao-Jun Chen, Yan-Hua Bi, Li-Hua Zhang |
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Rok vydání: | 2021 |
Předmět: |
Pharmacology
Acrylamides Cancer Research Aniline Compounds medicine.drug_class Kinase Janus kinase 3 Proteins Antineoplastic Agents Computational biology Network Pharmacology Biology Tyrosine-kinase inhibitor Molecular Docking Simulation Oncology medicine biology.protein Pharmacology (medical) Osimertinib Protein Interaction Maps Epidermal growth factor receptor Protein kinase A Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
Zdroj: | Anti-Cancer Drugs. 33:e434-e443 |
ISSN: | 0959-4973 |
Popis: | Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor used to treat non-small cell lung cancer. However, its off-targets are obscure, and systematic analysis of off-target activities remains to be performed. Here, we identified the off-targets of osimertinib using PharmMapper and DRAR-CPI and analyzed the intersected targets using the GeneMANIA and DAVID servers. A drug-target-pathway network was constructed to visualize the associations. The results showed that osimertinib is associated with 31 off-targets, 40 Kyoto Encyclopedia of Genes and Genomes pathways, and 9 diseases. Network analysis revealed that the targets were involved in cancer and other physiological processes. In addition to EGFR, molecular docking analysis showed that seven proteins, namely Janus kinase 3, peroxisome proliferator-activated receptor alpha, renin, mitogen-activated protein kinases, lymphocyte-specific protein tyrosine kinase, cell division protein kinase 2 and proto-oncogene tyrosine-protein kinase Src, could also be potential targets of osimertinib. In conclusion, osimertinib is predicted to target multiple proteins and pathways, resulting in the formation of an action network via which it exerts systematic pharmacological effects. |
Databáze: | OpenAIRE |
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