The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors
Isocitrate dehydrogenases constitute a class of enzymes that are crucial for cellular metabolism. The overexpression or mutation of isocitrate dehydrogenases are often found in leukemias, glioblastomas, lung cancers, and ductal pancreatic cancer among others. Mutation R132H, which changes the functi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/3/536 |
| _version_ | 1797709097416523776 |
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| author | Katarzyna Malarz Jacek Mularski Marcin Pacholczyk Robert Musiol |
| author_facet | Katarzyna Malarz Jacek Mularski Marcin Pacholczyk Robert Musiol |
| author_sort | Katarzyna Malarz |
| collection | DOAJ |
| description | Isocitrate dehydrogenases constitute a class of enzymes that are crucial for cellular metabolism. The overexpression or mutation of isocitrate dehydrogenases are often found in leukemias, glioblastomas, lung cancers, and ductal pancreatic cancer among others. Mutation R132H, which changes the functionality of an enzyme to produce mutagenic 2-hydroxyglutarate instead of a normal product, is particularly important in this field. A series of inhibitors were described for these enzymes of which ivosidenib was the first to be approved for treating leukemia and bile duct cancers in 2018. Here, we investigated the polypharmacological landscape of the activity for known sulfamoyl derivatives that are inhibitors, which are selective towards IDH1 R132H. These compounds appeared to be effective inhibitors of several non-receptor kinases at a similar level as imatinib and axitinib. The antiproliferative activity of these compounds against a panel of cancer cells was tested and is explained based on the relative expression levels of the investigated proteins. The multitargeted activity of these compounds makes them valuable agents against a wide range of cancers, regardless of the status of IDH1. |
| first_indexed | 2024-03-12T06:32:24Z |
| format | Article |
| id | doaj.art-c7182cf43cbe4debbc602f6ce26a20f3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T06:32:24Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c7182cf43cbe4debbc602f6ce26a20f32023-09-03T01:34:56ZengMDPI AGCancers2072-66942020-02-0112353610.3390/cancers12030536cancers12030536The Landscape of the Anti-Kinase Activity of the IDH1 InhibitorsKatarzyna Malarz0Jacek Mularski1Marcin Pacholczyk2Robert Musiol3August Chełkowski Institute of Physics and Silesian Center for Education and Interdisciplinary Research, University of Silesia in Katowice, 75 Pułku Piechoty 1, 41-500 Chorzów, PolandInstitute of Chemistry, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500 Chorzów, PolandDepartment of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, PolandInstitute of Chemistry, University of Silesia in Katowice, 75 Pułku Piechoty 1A, 41-500 Chorzów, PolandIsocitrate dehydrogenases constitute a class of enzymes that are crucial for cellular metabolism. The overexpression or mutation of isocitrate dehydrogenases are often found in leukemias, glioblastomas, lung cancers, and ductal pancreatic cancer among others. Mutation R132H, which changes the functionality of an enzyme to produce mutagenic 2-hydroxyglutarate instead of a normal product, is particularly important in this field. A series of inhibitors were described for these enzymes of which ivosidenib was the first to be approved for treating leukemia and bile duct cancers in 2018. Here, we investigated the polypharmacological landscape of the activity for known sulfamoyl derivatives that are inhibitors, which are selective towards IDH1 R132H. These compounds appeared to be effective inhibitors of several non-receptor kinases at a similar level as imatinib and axitinib. The antiproliferative activity of these compounds against a panel of cancer cells was tested and is explained based on the relative expression levels of the investigated proteins. The multitargeted activity of these compounds makes them valuable agents against a wide range of cancers, regardless of the status of IDH1.https://www.mdpi.com/2072-6694/12/3/536isocitrate dehydrogenasetyrosine kinaseidh1 inhibitorabl kinase, leukemiaanticancer activity |
| spellingShingle | Katarzyna Malarz Jacek Mularski Marcin Pacholczyk Robert Musiol The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors Cancers isocitrate dehydrogenase tyrosine kinase idh1 inhibitor abl kinase, leukemia anticancer activity |
| title | The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors |
| title_full | The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors |
| title_fullStr | The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors |
| title_full_unstemmed | The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors |
| title_short | The Landscape of the Anti-Kinase Activity of the IDH1 Inhibitors |
| title_sort | landscape of the anti kinase activity of the idh1 inhibitors |
| topic | isocitrate dehydrogenase tyrosine kinase idh1 inhibitor abl kinase, leukemia anticancer activity |
| url | https://www.mdpi.com/2072-6694/12/3/536 |
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