Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery
Hexoses are the major source of energy and carbon skeletons for biosynthetic processes in all kingdoms of life. Their cellular uptake is mediated by specialized transporters, including glucose transporters (GLUT, SLC2 gene family). Malfunction or altered expression pattern of GLUTs in humans is asso...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2018.00183/full |
| _version_ | 1819206783100518400 |
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| author | Sina Schmidl Cristina V. Iancu Jun-yong Choe Mislav Oreb |
| author_facet | Sina Schmidl Cristina V. Iancu Jun-yong Choe Mislav Oreb |
| author_sort | Sina Schmidl |
| collection | DOAJ |
| description | Hexoses are the major source of energy and carbon skeletons for biosynthetic processes in all kingdoms of life. Their cellular uptake is mediated by specialized transporters, including glucose transporters (GLUT, SLC2 gene family). Malfunction or altered expression pattern of GLUTs in humans is associated with several widespread diseases including cancer, diabetes and severe metabolic disorders. Their high relevance in the medical area makes these transporters valuable drug targets and potential biomarkers. Nevertheless, the lack of a suitable high-throughput screening system has impeded the determination of compounds that would enable specific manipulation of GLUTs so far. Availability of structural data on several GLUTs enabled in silico ligand screening, though limited by the fact that only two major conformations of the transporters can be tested. Recently, convenient high-throughput microbial and cell-free screening systems have been developed. These remarkable achievements set the foundation for further and detailed elucidation of the molecular mechanisms of glucose transport and will also lead to great progress in the discovery of GLUT effectors as therapeutic agents. In this mini-review, we focus on recent efforts to identify potential GLUT-targeting drugs, based on a combination of structural biology and different assay systems. |
| first_indexed | 2024-12-23T05:13:05Z |
| format | Article |
| id | doaj.art-ba7c6b6440f0421e9ee4dfe08d1878aa |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-23T05:13:05Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-ba7c6b6440f0421e9ee4dfe08d1878aa2022-12-21T17:58:55ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-05-01610.3389/fchem.2018.00183371069Ligand Screening Systems for Human Glucose Transporters as Tools in Drug DiscoverySina Schmidl0Cristina V. Iancu1Jun-yong Choe2Mislav Oreb3Institute of Molecular Biosciences, Goethe University Frankfurt, Frankfurt am Main, GermanyDepartment of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesDepartment of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United StatesInstitute of Molecular Biosciences, Goethe University Frankfurt, Frankfurt am Main, GermanyHexoses are the major source of energy and carbon skeletons for biosynthetic processes in all kingdoms of life. Their cellular uptake is mediated by specialized transporters, including glucose transporters (GLUT, SLC2 gene family). Malfunction or altered expression pattern of GLUTs in humans is associated with several widespread diseases including cancer, diabetes and severe metabolic disorders. Their high relevance in the medical area makes these transporters valuable drug targets and potential biomarkers. Nevertheless, the lack of a suitable high-throughput screening system has impeded the determination of compounds that would enable specific manipulation of GLUTs so far. Availability of structural data on several GLUTs enabled in silico ligand screening, though limited by the fact that only two major conformations of the transporters can be tested. Recently, convenient high-throughput microbial and cell-free screening systems have been developed. These remarkable achievements set the foundation for further and detailed elucidation of the molecular mechanisms of glucose transport and will also lead to great progress in the discovery of GLUT effectors as therapeutic agents. In this mini-review, we focus on recent efforts to identify potential GLUT-targeting drugs, based on a combination of structural biology and different assay systems.https://www.frontiersin.org/article/10.3389/fchem.2018.00183/fullglucose transportsugar transport inhibitorsscreening systemsugar transport assaysdrug discoveryhxt0 strain |
| spellingShingle | Sina Schmidl Cristina V. Iancu Jun-yong Choe Mislav Oreb Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery Frontiers in Chemistry glucose transport sugar transport inhibitors screening system sugar transport assays drug discovery hxt0 strain |
| title | Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery |
| title_full | Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery |
| title_fullStr | Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery |
| title_full_unstemmed | Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery |
| title_short | Ligand Screening Systems for Human Glucose Transporters as Tools in Drug Discovery |
| title_sort | ligand screening systems for human glucose transporters as tools in drug discovery |
| topic | glucose transport sugar transport inhibitors screening system sugar transport assays drug discovery hxt0 strain |
| url | https://www.frontiersin.org/article/10.3389/fchem.2018.00183/full |
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