MKK4 Inhibitors—Recent Development Status and Therapeutic Potential
MKK4 (mitogen-activated protein kinase kinase 4; also referred to as MEK4) is a dual-specificity protein kinase that phosphorylates and regulates both JNK (c-Jun N-terminal kinase) and p38 MAPK (p38 mitogen-activated protein kinase) signaling pathways and therefore has a great impact on cell prolife...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7495 |
| _version_ | 1797605093579685888 |
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| author | Leon Katzengruber Pascal Sander Stefan Laufer |
| author_facet | Leon Katzengruber Pascal Sander Stefan Laufer |
| author_sort | Leon Katzengruber |
| collection | DOAJ |
| description | MKK4 (mitogen-activated protein kinase kinase 4; also referred to as MEK4) is a dual-specificity protein kinase that phosphorylates and regulates both JNK (c-Jun N-terminal kinase) and p38 MAPK (p38 mitogen-activated protein kinase) signaling pathways and therefore has a great impact on cell proliferation, differentiation and apoptosis. Overexpression of MKK4 has been associated with aggressive cancer types, including metastatic prostate and ovarian cancer and triple-negative breast cancer. In addition, MKK4 has been identified as a key regulator in liver regeneration. Therefore, MKK4 is a promising target both for cancer therapeutics and for the treatment of liver-associated diseases, offering an alternative to liver transplantation. The recent reports on new inhibitors, as well as the formation of a startup company investigating an inhibitor in clinical trials, show the importance and interest of MKK4 in drug discovery. In this review, we highlight the significance of MKK4 in cancer development and other diseases, as well as its unique role in liver regeneration. Furthermore, we present the most recent progress in MKK4 drug discovery and future challenges in the development of MKK4-targeting drugs. |
| first_indexed | 2024-03-11T04:56:16Z |
| format | Article |
| id | doaj.art-901c4f043f724ab996df75fad6c0677f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:56:16Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-901c4f043f724ab996df75fad6c0677f2023-11-17T19:41:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248749510.3390/ijms24087495MKK4 Inhibitors—Recent Development Status and Therapeutic PotentialLeon Katzengruber0Pascal Sander1Stefan Laufer2Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Faculty of Sciences, University of Tuebingen, 72076 Tübingen, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Faculty of Sciences, University of Tuebingen, 72076 Tübingen, GermanyDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Faculty of Sciences, University of Tuebingen, 72076 Tübingen, GermanyMKK4 (mitogen-activated protein kinase kinase 4; also referred to as MEK4) is a dual-specificity protein kinase that phosphorylates and regulates both JNK (c-Jun N-terminal kinase) and p38 MAPK (p38 mitogen-activated protein kinase) signaling pathways and therefore has a great impact on cell proliferation, differentiation and apoptosis. Overexpression of MKK4 has been associated with aggressive cancer types, including metastatic prostate and ovarian cancer and triple-negative breast cancer. In addition, MKK4 has been identified as a key regulator in liver regeneration. Therefore, MKK4 is a promising target both for cancer therapeutics and for the treatment of liver-associated diseases, offering an alternative to liver transplantation. The recent reports on new inhibitors, as well as the formation of a startup company investigating an inhibitor in clinical trials, show the importance and interest of MKK4 in drug discovery. In this review, we highlight the significance of MKK4 in cancer development and other diseases, as well as its unique role in liver regeneration. Furthermore, we present the most recent progress in MKK4 drug discovery and future challenges in the development of MKK4-targeting drugs.https://www.mdpi.com/1422-0067/24/8/7495MKK4MEK4MAP2K4MAPKkinase inhibitorsdrug design |
| spellingShingle | Leon Katzengruber Pascal Sander Stefan Laufer MKK4 Inhibitors—Recent Development Status and Therapeutic Potential International Journal of Molecular Sciences MKK4 MEK4 MAP2K4 MAPK kinase inhibitors drug design |
| title | MKK4 Inhibitors—Recent Development Status and Therapeutic Potential |
| title_full | MKK4 Inhibitors—Recent Development Status and Therapeutic Potential |
| title_fullStr | MKK4 Inhibitors—Recent Development Status and Therapeutic Potential |
| title_full_unstemmed | MKK4 Inhibitors—Recent Development Status and Therapeutic Potential |
| title_short | MKK4 Inhibitors—Recent Development Status and Therapeutic Potential |
| title_sort | mkk4 inhibitors recent development status and therapeutic potential |
| topic | MKK4 MEK4 MAP2K4 MAPK kinase inhibitors drug design |
| url | https://www.mdpi.com/1422-0067/24/8/7495 |
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