Fiche publication
Date publication
septembre 2022
Journal
Bioconjugate chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah
,
Dr WAGNER Alain
,
Dr CHAUBET Guilhem
Tous les auteurs :
Rady T, Turelli L, Nothisen M, Tobaldi E, Erb S, Thoreau F, Hernandez-Alba O, Cianferani S, Daubeuf F, Wagner A, Chaubet G
Lien Pubmed
Résumé
Cleavable linkers have become the subject of intense study in the field of chemical biology, particularly because of their applications in the construction of antibody-drug conjugates (ADC), where they facilitate lysosomal cleavage and liberation of drugs from their carrier protein. Due to lysosomes' acidic nature, acid-labile motifs have attracted much attention, leading to the development of hydrazone and carbonate linkers among several other entities. Continuing our efforts in designing new moieties, we present here a family of cyclic acetals that exhibit excellent plasma stability and acid lability, notably in lysosomes. Incorporated in ADC, they led to potent constructs with picomolar potency in vitro and similar in vivo efficacy as the commercially available ADC Kadcyla in mouse xenograft models.
Référence
Bioconjug Chem. 2022 09 15;:
