{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:20:12Z","timestamp":1721089212187},"reference-count":68,"publisher":"EDP Sciences","issue":"1-2","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":196,"URL":"https:\/\/www.edpsciences.org\/en\/authors\/copyright-and-licensing"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biologie Aujourd\u2019hui"],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:p>La recherche dans le domaine de la d\u00e9gradation cibl\u00e9e des prot\u00e9ines s\u2019est consid\u00e9rablement d\u00e9velopp\u00e9e conduisant \u00e0 l\u2019\u00e9laboration de nouveaux outils chimiques \u00e0 vis\u00e9e th\u00e9rapeutique, les d\u00e9gradeurs, potentiellement utiles dans diverses pathologies. Une grande vari\u00e9t\u00e9 d\u2019objets \u00e0 d\u00e9grader appartenant \u00e0 divers compartiments intra- ou extracellulaires (prot\u00e9ines, complexes ou agr\u00e9gats, organelles, acides nucl\u00e9iques, gouttelettes lipidiques) a \u00e9t\u00e9 cibl\u00e9e \u00e0 l\u2019aide de ligands d\u00e9j\u00e0 existants, d\u2019autres restent \u00e0 d\u00e9couvrir. Les mol\u00e9cules de premi\u00e8re g\u00e9n\u00e9ration, PROTAC et colles mol\u00e9culaires, utilisent le syst\u00e8me ubiquitine-prot\u00e9asome pour d\u00e9truire sp\u00e9cifiquement des prot\u00e9ines pathog\u00e9niques, certaines consid\u00e9r\u00e9es jusqu\u2019\u00e0 pr\u00e9sent comme inaccessibles en tant que cibles th\u00e9rapeutiques. Au cours des cinq derni\u00e8res ann\u00e9es, ont \u00e9t\u00e9 d\u00e9velopp\u00e9s de nouveaux types de PROTAC h\u00e9t\u00e9ro-bifonctionnels comme les homo-PROTAC, pro-PROTAC, CLIPTAC, HaloPROTAC, PHOTOTAC, Bac-PROTAC, mais aussi des PROTAC macromol\u00e9culaires comme les AbTAC et ARN-PROTAC. Du fait de la grande diversit\u00e9 des substrats d\u00e9grad\u00e9s par les lysosomes, de nouveaux d\u00e9gradeurs impliquant deux voies distinctes ont \u00e9t\u00e9 ensuite produits\u00a0: les chim\u00e8res LYTAC pour la voie endosome-lysosome et les chim\u00e8res ATTEC, AUTAC et AUTOTAC pour la voie autophagie-lysosome, augmentant ainsi consid\u00e9rablement le champ d\u2019action des d\u00e9gradeurs. Ces nouvelles mol\u00e9cules reconnaissent sp\u00e9cifiquement des prot\u00e9ines et\/ou des organelles et permettent leur transport dans les lysosomes o\u00f9 ils sont d\u00e9grad\u00e9s. Les succ\u00e8s obtenus, que ce soit par d\u00e9gradation prot\u00e9asomale ou lysosomale pour plusieurs dizaines de d\u00e9gradeurs (preuves de concepts et \u00e9tudes cliniques en cours), expliquent l\u2019int\u00e9r\u00eat quasi mondial des industries pharmaceutiques pour ces nouvelles mol\u00e9cules. Les challenges pos\u00e9s par leur d\u00e9veloppement et leur utilisation en clinique sont discut\u00e9s.<\/jats:p>","DOI":"10.1051\/jbio\/2024007","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T08:05:13Z","timestamp":1721030713000},"page":"41-54","source":"Crossref","is-referenced-by-count":0,"title":["Induction de proximit\u00e9 et d\u00e9gradation de cibles th\u00e9rapeutiques par les nouveaux d\u00e9gradeurs\u00a0: quels concepts, quels d\u00e9veloppements, quel futur\u00a0?"],"prefix":"10.1051","volume":"218","author":[{"given":"Miche\u0300le","family":"Reboud-Ravaux","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"250","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1038\/s41591-023-02635-7","volume":"29","author":"Ackerman","year":"2023","journal-title":"Nature 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