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Author

A. Scrima

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Sep 2026

Covalent-Allosteric Akt Inhibitors: Targeting Akt3 through Molecular Hybridization and Expanding the Isoform-Selective Toolbox.

Akt is a central serine/threonine kinase in the PI3K/Akt/mTOR pathway that regulates cell survival, growth, and metabolic homeostasis. Although Akt1, Akt2, and Akt3 share high sequence homology, they perform distinct physiological and pathological functions, motivating the development of small-molecule isoform-selectiv...

Kosmas Alexandros Pervanidis, G. D'Angelo, Ioannis Athanasiadis et al. · 0 citations
Open access Aug 2026

Structure-based scaffold hopping reveals strategies to overcome oncogenic KIT and PDGFRA mutation-driven drug-resistance in GIST

A structure-based scaffold-hopping strategy to design kinase inhibitors with selectivity for mutant KIT/PDGFRA and the PDGFRA-G680R structure shows the molecular basis for targeting solvent-front mutations across oncogenic kinases.

T. Schulz, M. Beerbaum, A. Scrima et al. · 0 citations
Sep 2026

Isoform-Selective Targeting of Akt Through Covalent Allosteric Inhibition.

Developing selective covalent-allosteric Akt inhibitors targeting Akt2 and Akt3 while sparing Akt1 is reported, which establishes a framework for the development of isoform-selective therapeutics and highlights the potential for unraveling isoform-specific functions in signaling pathways relevant to cancer biology.

G. D'Angelo, Kosmas Alexandros Pervanidis, Ioannis Athanasiadis et al. · 1 citation

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