Nintedanib-Containing Dual Conjugates Targeting α_Vβ₆ Integrin and Tyrosine Kinase Receptors as Potential Antifibrotic Agents.

ABSTRACT: α_Vβ₆ Integrin plays a fundamental role in the activation of transforming growth factor-β (TGF-β), the major profibrotic mediator; for this reason, α_Vβ₆ ligands have recently been forwarded to clinical phases for the therapy of fibrotic diseases. Herein, we report the synthesis and in vitro biological evaluation as antifibrotic agents of three new covalent conjugates, constituted by c(AmpLRGDL), an α_Vβ₆ integrin-recognizing small cyclopeptide, and nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF) treatment. One of these conjugates recapitulates optimal in vitro antifibrotic properties of the two active units. The integrin ligand portion within the conjugate plays a r

SUBMITTER: Bugatti K 

PROVIDER: S-EPMC9161413 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature