Different chemical proteomic approaches to identify the targets of lapatinib
AbstractThe process of identifying the protein targets and off-targets of a biologically active compound is of great importance in modern drug discovery. Various chemical proteomics approaches have been established for this purpose. To compare the different approaches, and to understand which method...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2183809 |
| _version_ | 1797400915244744704 |
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| author | Tatjana Kovačević Krunoslav Nujić Mario Cindrić Snježana Dragojević Adrijana Vinter Amela Hozić Milan Mesić |
| author_facet | Tatjana Kovačević Krunoslav Nujić Mario Cindrić Snježana Dragojević Adrijana Vinter Amela Hozić Milan Mesić |
| author_sort | Tatjana Kovačević |
| collection | DOAJ |
| description | AbstractThe process of identifying the protein targets and off-targets of a biologically active compound is of great importance in modern drug discovery. Various chemical proteomics approaches have been established for this purpose. To compare the different approaches, and to understand which method would provide the best results, we have chosen the EGFR inhibitor lapatinib as an example molecule. Lapatinib derivatives were designed using linkers with motifs, including amino (amidation), alkyne (click chemistry) and the diazirine group (photo-affinity). These modified lapatinib analogues were validated for their ability to inhibit EGFR activity in vitro and were shown to pull down purified recombinant EGFR protein. In all of the approaches evaluated here, we identified EGFR as the main protein target from the lysate of immortalised cell line expressing EGFR, thus validating its potential use to identify unknown protein targets. Taken together, the results reported here give insight into the cellular activities of lapatinib. |
| first_indexed | 2024-03-09T02:02:26Z |
| format | Article |
| id | doaj.art-0e9e0eecf46f428088a5bbe0540be1c8 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:26Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-0e9e0eecf46f428088a5bbe0540be1c82023-12-08T03:24:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2183809Different chemical proteomic approaches to identify the targets of lapatinibTatjana Kovačević0Krunoslav Nujić1Mario Cindrić2Snježana Dragojević3Adrijana Vinter4Amela Hozić5Milan Mesić6Selvita Ltd., Zagreb, CroatiaSelvita Ltd., Zagreb, CroatiaRuđer Bošković Institute, Zagreb, CroatiaSelvita Ltd., Zagreb, CroatiaSelvita Ltd., Zagreb, CroatiaRuđer Bošković Institute, Zagreb, CroatiaSelvita Ltd., Zagreb, CroatiaAbstractThe process of identifying the protein targets and off-targets of a biologically active compound is of great importance in modern drug discovery. Various chemical proteomics approaches have been established for this purpose. To compare the different approaches, and to understand which method would provide the best results, we have chosen the EGFR inhibitor lapatinib as an example molecule. Lapatinib derivatives were designed using linkers with motifs, including amino (amidation), alkyne (click chemistry) and the diazirine group (photo-affinity). These modified lapatinib analogues were validated for their ability to inhibit EGFR activity in vitro and were shown to pull down purified recombinant EGFR protein. In all of the approaches evaluated here, we identified EGFR as the main protein target from the lysate of immortalised cell line expressing EGFR, thus validating its potential use to identify unknown protein targets. Taken together, the results reported here give insight into the cellular activities of lapatinib.https://www.tandfonline.com/doi/10.1080/14756366.2023.2183809Chemical proteomicsaffinity chromatographydiazirinesphotoaffinity labellingEGFRlapatinib |
| spellingShingle | Tatjana Kovačević Krunoslav Nujić Mario Cindrić Snježana Dragojević Adrijana Vinter Amela Hozić Milan Mesić Different chemical proteomic approaches to identify the targets of lapatinib Journal of Enzyme Inhibition and Medicinal Chemistry Chemical proteomics affinity chromatography diazirines photoaffinity labelling EGFR lapatinib |
| title | Different chemical proteomic approaches to identify the targets of lapatinib |
| title_full | Different chemical proteomic approaches to identify the targets of lapatinib |
| title_fullStr | Different chemical proteomic approaches to identify the targets of lapatinib |
| title_full_unstemmed | Different chemical proteomic approaches to identify the targets of lapatinib |
| title_short | Different chemical proteomic approaches to identify the targets of lapatinib |
| title_sort | different chemical proteomic approaches to identify the targets of lapatinib |
| topic | Chemical proteomics affinity chromatography diazirines photoaffinity labelling EGFR lapatinib |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2183809 |
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