任天堂
结合
癌症研究
药理学
化学
酪氨酸激酶
受体
医学
生物化学
内科学
特发性肺纤维化
肺
数学分析
数学
作者
Kelly Bugatti,Elena Andreucci,Noemi Monaco,Lucia Battistini,Silvia Peppicelli,Jessica Ruzzolini,Claudio Curti,Franca Zanardi,Francesca Bianchini,Andrea Sartori
出处
期刊:ACS omega
[American Chemical Society]
日期:2022-05-17
卷期号:7 (21): 17658-17669
被引量:6
标识
DOI:10.1021/acsomega.2c00535
摘要
αVβ6 Integrin plays a fundamental role in the activation of transforming growth factor-β (TGF-β), the major profibrotic mediator; for this reason, αVβ6 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 αVβ6 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 role in inhibiting profibrotic stimuli, potentiating the nintedanib effect and favoring the selective uptake of the conjugate in cells overexpressing αVβ6 integrin. These results may open a new perspective on the development of dual conjugates in the targeted therapy of IPF.
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