Design and synthesis of a new, conformationally constrained, macrocyclic small-molecule inhibitor of STAT3 via ‘click chemistry’

STAT3 is a promising molecular target for the design of new anticancer drugs. In this paper, we report the design and synthesis of a conformationally constrained macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to bind to STAT3 with a Ki value of 7.3 μM in a competitive fluorescence-polarization-based binding assay, representing a promising initial lead compound for further optimization.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide