Targeting the non-canonical G protein signaling via Girdin inhibition: from ligand to tracer development
Anna Junker

Girdin (GIV) is a key activator of Gi proteins that links RTK and GPCR signaling to PI3K-Akt activation and reduced cAMP levels, driving processes like cell migration and metastasis; its overexpression in cancers makes it a promising therapeutic target, and the recently discovered selective inhibitor IGGi-11 offers the first proof-of-concept for pharmacologically blocking Girdin-mediated tumor progression.

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Our project aims to develop improved inhibitors of the Girdin–Gαi interaction based on the first-in-class compound IGGi-11. By optimizing its structure for metabolic stability and bioavailability, we seek to create potent anti-cancer candidates and radiolabeled PET tracers to enable both therapy and imaging of Girdin-driven tumors.