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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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
August 2023
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| In: |
Molecular therapy
Year: 2023, Jahrgang: 31, Heft: 8, Pages: 2408-2421 |
| ISSN: | 1525-0024 |
| DOI: | 10.1016/j.ymthe.2023.06.020 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 520 | |a 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. ... | ||
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