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Development of a peptide drug restoring AMPK and adipose tissue functionality in cancer cachexia

Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in...

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Main Authors: Ji, Honglei (Author) , Englmaier, Felix (Author) , Morigny, Pauline (Author) , Giroud, Maude (Author) , Gräsle, Pamina (Author) , Brings, Sebastian (Author) , Szendrödi, Julia (Author) , Berriel Diaz, Mauricio (Author) , Plettenburg, Oliver (Author) , Herzig, Stephan (Author) , Rohm, Maria (Author)
Format: Article (Journal)
Language:English
Published: August 2023
In: Molecular therapy
Year: 2023, Volume: 31, Issue: 8, Pages: 2408-2421
ISSN:1525-0024
DOI:10.1016/j.ymthe.2023.06.020
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ymthe.2023.06.020
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1525001623003805
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Author Notes:Honglei Ji, Felix Englmaier, Pauline Morigny, Maude Giroud, Pamina Gräsle, Sebastian Brings, Julia Szendrödi, Mauricio Berriel Diaz, Oliver Plettenburg, Stephan Herzig, and Maria Rohm
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Summary:Cancer cachexia is a severe systemic wasting disease that negatively affects quality of life and survival in patients with cancer. To date, treating cancer cachexia is still a major unmet clinical need. We recently discovered the destabilization of the AMP-activated protein kinase (AMPK) complex in adipose tissue as a key event in cachexia-related adipose tissue dysfunction and developed an adeno-associated virus (AAV)-based approach to prevent AMPK degradation and prolong cachexia-free survival. Here, we show the development and optimization of a prototypic peptide, Pen-X-ACIP, where the AMPK-stabilizing peptide ACIP is fused to the cell-penetrating peptide moiety penetratin via a propargylic glycine linker to enable late-stage functionalization using click chemistry. ...
Item Description:Online veröffentlicht am 4. Juli 2023
Gesehen am 07.12.2023
Physical Description:Online Resource
ISSN:1525-0024
DOI:10.1016/j.ymthe.2023.06.020

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