A Comprehensive <i>In Vitro</i> Characterization of a New Class of Indole-Based Compounds Developed as Selective Haspin Inhibitors.

ABSTRACT: Haspin is an emerging, but rather unexplored, divergent kinase involved in tumor growth by regulating the mitotic phase. In this paper, the in-silico design, synthesis, and biological characterization of a new series of substituted indoles acting as potent Haspin inhibitors are reported. The synthesized derivatives have been evaluated by FRET analysis, showing very potent Haspin inhibition. Then, a comprehensive in-cell investigation highlighted compounds 47 and 60 as the most promising inhibitors. These compounds were challenged for their synergic activity with paclitaxel in 2D and 3D cellular models, demonstrating a twofold improvement of the paclitaxel antitumor activity. Compound 60 also showed remarkable selectivity when tested in a panel of 70 diverse kina

SUBMITTER: Vestuto V 

PROVIDER: S-EPMC11320660 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature