Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024;218(3-4):105-113.
doi: 10.1051/jbio/2024010. Epub 2025 Jan 27.

[Exploring protein degradation pathways as therapeutic innovations]

[Article in French]
Marie Cornu  1 , Thomas Lemaitre  1 , Florian Schwalen  2 , Charline Kieffer  1 , Anne Sophie Voisin-Chiret  1
Affiliations
Review

[Exploring protein degradation pathways as therapeutic innovations]

[Article in French]
Marie Cornu et al. Biol Aujourdhui. 2024.

Abstract
in English, French

The disruption of proteostasis provides a favourable context for the emergence of therapeutic innovations, in particular by exploiting technologies such as the PROTAC (Proteolysis Targeting Chimera) approach. These technologies aim to selectively target proteins involved in various diseases, including cancer and neurodegenerative diseases, by inducing their specific degradation via the ubiquitin-proteasome system. The PROTAC approach opens new opportunities for restoring altered protein homeostasis and modulating the pathological consequences of proteostasis deregulation. In addition, by targeting proteins that are resistant to conventional therapeutic approaches, this new strategy offers a hope of treatment. By degrading target proteins, regardless of their structure or of mutations, the PROTAC approach opens the way to reaching previously inaccessible targets and reducing resistance to treatment.

Title: PROTAC : Nouvelles stratégies thérapeutiques basées sur l’exploitation des voies de dégradation des protéines.

Abstract: La perturbation de la protéostasie constitue un contexte propice à l’innovation thérapeutique, en particulier grâce à l’exploitation de technologies comme l’approche PROTAC (Proteolysis Targeting Chimera). Cette technologie vise à cibler sélectivement des protéines impliquées dans diverses maladies, dont le cancer et les maladies neurodégénératives, en induisant leur dégradation spécifique via le système ubiquitine-protéasome. Ainsi, l’approche PROTAC ouvre de nouvelles perspectives pour restaurer l’homéostasie protéique altérée, et moduler les conséquences pathologiques induites par la dérégulation de la protéostasie. De plus, en ciblant des protéines résistantes aux approches thérapeutiques classiques, cette nouvelle stratégie offre un espoir de traitement. En dégradant des protéines cibles, indépendamment de leur forme ou de mutations, l’approche PROTAC ouvre la voie à l’atteinte de cibles auparavant inaccessibles et à la réduction de la résistance au traitement.

Keywords: E3 ubiquitin ligase; PROTAC; chimie médicinale; interactions protéine-protéine; medicinal chemistry; protein-protein interactions; proteostasis; protéostasie; ubiquitine ligase E3.

PubMed Disclaimer

References

    1. Anwar, Z., Ali, M.S., Galvano, A., Perez, A., La Mantia, M., Bukhari, I., et al. (2022). PROTACs: The future of leukemia therapeutics. Front Cell Dev Biol, 10, 851087.
    1. Apprato, G., Ermondi, G., Caron, C. (2023). The quest for oral PROTAC drugs: Evaluating the weaknesses of the screening pipeline. ACS Med Chem Lett, 14, 879-883.
    1. Atilaw, Y., Poongavanam, V., Svensson Nilsson, C., Nguyen, D., Giese, A., Meibom, D., et al. (2021). Solution conformations shed light on PROTAC cell permeability. ACS Med Chem Lett, 12, 107-114.
    1. Békés, M., Langley, D.R., Crews, C.M. (2022). PROTAC targeted protein degraders: The past is prologue. Nat Rev Drug Discov, 21, 181-200.
    1. Chopra, R., Sadok, A., Collins, I. (2019). A critical evaluation of the approaches to targeted protein degradation for drug discovery. Drug Discov Today Technol, 31, 5-13.

MeSH terms