Targeting IAP proteins for therapeutic intervention in cancer

By Simone Fulda, D. Vučić. Nature reviews. Drug discovery, 2012

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Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “inhibitors) [337], RIPK1 is deubiquitinated by CYLD lysine”
Mitochondrial apoptosis: killing cancer using the enemy within (2015, background): “These include death-receptor ligands, notably TRAIL, that trigger the extrinsic apoptotic pathway and SMAC-mimetics, that were designed to enhance caspase activation (Fulda and Vucic, 2012; Lemke et al, 2014).”
Caspases in Cell Death, Inflammation, and Gasdermin-Induced Pyroptosis (2020, background): “Overexpression of cIAPs in multiple cancer types confers resistance of cancer cells to apoptotic cell death activation (179).”
Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. (2014, background): “High-resolution structures in the 1980s to 1990s showed that PPI interfaces are generally flat and large (roughly 1,000–2,000 A2 per side) (Hwang et al., 2010), in stark contrast to the deep cavities that typically bind small molecules ( 300–500 A2) (Fuller et al., 2009).”
PROteolysis TArgeting Chimeras (PROTACs) - Past, Present and Future (2019, background): “First, the originally used cIAP1 ligands suffered from specificity issues and caused cIAP1 degradation which made the utility of this E3 somewhat self-limiting [91,92].”