Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review
Maternal embryonic leucine zipper kinase (MELK), a member of the AMP-related serine-threonine kinase family, has been involved in regulating many cellular events, and aberrant MELK expression is associated with tumorigenesis and malignant progression in various cancers. More and more studies have fo...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222013543 |
| _version_ | 1811180263154122752 |
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| author | Ling Ren Jing-si Guo Yu-heng Li Gang Dong Xin-yang Li |
| author_facet | Ling Ren Jing-si Guo Yu-heng Li Gang Dong Xin-yang Li |
| author_sort | Ling Ren |
| collection | DOAJ |
| description | Maternal embryonic leucine zipper kinase (MELK), a member of the AMP-related serine-threonine kinase family, has been involved in regulating many cellular events, and aberrant MELK expression is associated with tumorigenesis and malignant progression in various cancers. More and more studies have found that MELK plays an essential regulatory role in tumor multidrug resistance or radio resistance. MELK inhibitors can also improve drug resistance caused by a gene mutation. These findings remind us that MELK could be a chemo- or radio-sensitizing target. However, it has also been found that most experiments on MELK rely on non-selective RNAi and small molecule reagents, which makes the results questionable, and thus the development of selective MELK inhibitors is still necessary. In this review, we summarized the identified regulatory pathways of MELK in tumor resistance and reclassified MELK inhibitors from a structural perspective. In addition, we discovered the glycosylation modification site of the MELK protein and discussed the possibility of continuing to develop small molecule inhibitors targeting the glycosylation modification site. These provide new strategies for developing selective MELK inhibitors and understanding the essential biological role of MELK in cancer. |
| first_indexed | 2024-04-11T06:47:27Z |
| format | Article |
| id | doaj.art-d72fbb81af3b4942939a9fa0c6cdc7b2 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T06:47:27Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-d72fbb81af3b4942939a9fa0c6cdc7b22022-12-22T04:39:19ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113965Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A reviewLing Ren0Jing-si Guo1Yu-heng Li2Gang Dong3Xin-yang Li4Department of Anorectal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, PR ChinaDepartment of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, PR ChinaSchool of Pharmacy, China Medical University, Shenyang 110122, PR ChinaSchool of Pharmacy, China Medical University, Shenyang 110122, PR ChinaDepartment of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, PR China; Correspondence to: Shengjing Hospital of China Medical University, Shenyang 110004, PR China.Maternal embryonic leucine zipper kinase (MELK), a member of the AMP-related serine-threonine kinase family, has been involved in regulating many cellular events, and aberrant MELK expression is associated with tumorigenesis and malignant progression in various cancers. More and more studies have found that MELK plays an essential regulatory role in tumor multidrug resistance or radio resistance. MELK inhibitors can also improve drug resistance caused by a gene mutation. These findings remind us that MELK could be a chemo- or radio-sensitizing target. However, it has also been found that most experiments on MELK rely on non-selective RNAi and small molecule reagents, which makes the results questionable, and thus the development of selective MELK inhibitors is still necessary. In this review, we summarized the identified regulatory pathways of MELK in tumor resistance and reclassified MELK inhibitors from a structural perspective. In addition, we discovered the glycosylation modification site of the MELK protein and discussed the possibility of continuing to develop small molecule inhibitors targeting the glycosylation modification site. These provide new strategies for developing selective MELK inhibitors and understanding the essential biological role of MELK in cancer.http://www.sciencedirect.com/science/article/pii/S0753332222013543Tumor resistanceMELKO-GlcNAcCADD |
| spellingShingle | Ling Ren Jing-si Guo Yu-heng Li Gang Dong Xin-yang Li Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review Biomedicine & Pharmacotherapy Tumor resistance MELK O-GlcNAc CADD |
| title | Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review |
| title_full | Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review |
| title_fullStr | Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review |
| title_full_unstemmed | Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review |
| title_short | Structural classification of MELK inhibitors and prospects for the treatment of tumor resistance: A review |
| title_sort | structural classification of melk inhibitors and prospects for the treatment of tumor resistance a review |
| topic | Tumor resistance MELK O-GlcNAc CADD |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222013543 |
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