Synthesis of Indomorphan Pseudo‐Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3
Abstract: Bioactive compound design based on natural product (NP) structure may be limited because of partial coverage of NP‐like chemical space and biological target space. These limitations can be overcome by combining NP‐centered strategies with fragment‐based compound design through combination of NP‐derived fragments to afford structurally unprecedented “pseudo‐natural products” (pseudo‐NPs). The design, synthesis, and biological evaluation of a collection of indomorphan pseudo‐NPs that combine biosynthetically unrelated indole‐ and morphan‐alkaloid fragments are described. Indomorphane derivative Glupin was identified as a potent inhibitor of glucose uptake by selectively targeting and upregulating glucose transporters GLUT‐1 and GLUT‐3. Glupin suppresses glycolysis, reduces the levels of glucose‐derived metabolites, and attenuates the growth of various cancer cell lines. Our findings underscore the importance of dual GLUT‐1 and GLUT‐3 inhibition to efficiently suppress tumor cell growth and the cellular rescue mechanism, which counteracts glucose scarcity.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Synthesis of Indomorphan Pseudo‐Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3 ; volume:58 ; number:47 ; year:2019 ; pages:17016-17025 ; extent:10
Angewandte Chemie / International edition. International edition ; 58, Heft 47 (2019), 17016-17025 (gesamt 10)
- Creator
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Ceballos, Javier
Schwalfenberg, Melanie
Karageorgis, George
Reckzeh, Elena S.
Sievers, Sonja
Ostermann, Claude
Pahl, Axel
Sellstedt, Magnus
Nowacki, Jessica
Carnero Corrales, Marjorie A.
Wilke, Julian
Laraia, Luca
Tschapalda, Kirsten
Metz, Malte
Sehr, Dominik A.
Brand, Silke
Winklhofer, Konstanze
Janning, Petra
Ziegler, Slava
Waldmann, Herbert
- DOI
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10.1002/anie.201909518
- URN
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urn:nbn:de:101:1-2022071211214403082714
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:33 AM CEST
Data provider
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Associated
- Ceballos, Javier
- Schwalfenberg, Melanie
- Karageorgis, George
- Reckzeh, Elena S.
- Sievers, Sonja
- Ostermann, Claude
- Pahl, Axel
- Sellstedt, Magnus
- Nowacki, Jessica
- Carnero Corrales, Marjorie A.
- Wilke, Julian
- Laraia, Luca
- Tschapalda, Kirsten
- Metz, Malte
- Sehr, Dominik A.
- Brand, Silke
- Winklhofer, Konstanze
- Janning, Petra
- Ziegler, Slava
- Waldmann, Herbert
Other Objects (12)
Synthesis of Indomorphan Pseudo‐Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3
Development of Glucose Transporter (GLUT) Inhibitors
Small‐Molecule Inhibition of Glucose Transporters GLUT‐1–4
Charakterisierung der Glucose-Transporter-Isoformen Glut-4 und Glut-1 aus Skelett- und Herzmuskelgewebe
Expression und prognostische Relevanz der Glucose-Transporter-Proteine Glut 1 bis Glut 4 im humanen Pankreaskarzinom
Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family
Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions
Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta
Facilitative glucose transporters
Engineered XylE as a tool for mechanistic investigation and ligand discovery of the glucose transporters GLUTs
Experimental Data: Density Gluts, Cortical Columns, Circuits, PseudoBD
Downregulation of the glucose transporter GLUT 1 in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice
Synthesis of Indomorphan Pseudo‐Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3
Development of Glucose Transporter (GLUT) Inhibitors
Small‐Molecule Inhibition of Glucose Transporters GLUT‐1–4
Charakterisierung der Glucose-Transporter-Isoformen Glut-4 und Glut-1 aus Skelett- und Herzmuskelgewebe
Expression und prognostische Relevanz der Glucose-Transporter-Proteine Glut 1 bis Glut 4 im humanen Pankreaskarzinom
Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family
Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions
Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta
Facilitative glucose transporters
Engineered XylE as a tool for mechanistic investigation and ligand discovery of the glucose transporters GLUTs
Experimental Data: Density Gluts, Cortical Columns, Circuits, PseudoBD
Downregulation of the glucose transporter GLUT 1 in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice
Synthesis of Indomorphan Pseudo‐Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3
Development of Glucose Transporter (GLUT) Inhibitors
Small‐Molecule Inhibition of Glucose Transporters GLUT‐1–4
Charakterisierung der Glucose-Transporter-Isoformen Glut-4 und Glut-1 aus Skelett- und Herzmuskelgewebe
Expression und prognostische Relevanz der Glucose-Transporter-Proteine Glut 1 bis Glut 4 im humanen Pankreaskarzinom
Evolutionary ancestry and novel functions of the mammalian glucose transporter (GLUT) family
Immunohistochemical expression of the glucose transporters Glut-1 and Glut-3 in human malignant melanomas and benign melanocytic lesions
Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta
Facilitative glucose transporters
Engineered XylE as a tool for mechanistic investigation and ligand discovery of the glucose transporters GLUTs
Experimental Data: Density Gluts, Cortical Columns, Circuits, PseudoBD