Team:
Federica Cossu, Mario Milani, Eloise Mastrangelo, Elisa Fagnani, Paolo Cocomazzi, Bianca Braggiotti
Collaborations:
Istituto Tumori of Milano
Inhibitor of Apoptosis Proteins (IAPs) are key oncological targets whose overexpression promotes survival and resistance to therapy. Through their BIR domains, they regulate NF-κB signaling and block apoptosis by sequestering caspases. Structure-guided studies enabled the design of patented Smac-mimetics targeting type II BIRs; however, resistance linked to type I BIRs remains a challenge.
To address this, we identified novel inhibitors through virtual screening, with candidates showing activity in vitro and in cell-based assays, including modulation of NF-κB and induction of cancer cell death. By integrating molecular insights with high-resolution approaches, we aim to overcome chemoresistance and advance precision anticancer therapies.
Funding:
AIRC-MFAG (2016-2020), AIRC-MFAG 2022-2026
