Biophysical Insights into the Binding Interactions of Inhibitors (ICA-1S/1T) Targeting Protein Kinase C-ι

• DOI: 10.20944/preprints202506.0281.v1
• Publication Date: 2025-06-05T01:44:56Z
• Authors: Radwan Ebna Noor; Shahedul Islam; Tracess Smalley; Dimitra Keramisanou; Aaron Joshua Astalos; James William Leahy; Ioannis Gelis; Mildred Acevedo-D...

The overexpression of atypical protein kinase C-iota (PKC-ι) is a biomarker for carcinogenesis in various cells, such as glioma, ovarian, renal, etc. manifesting potential drug target. In previous vitro studies, ICA-1S and ICA-1T, an experimental candidate inhibiting PKC-ι, has demonstrated its specificity promising efficacy against cancer cell types. Moreover, the vivo studies have low toxicity levels acute chronic murine models. Despite these prior developments, binding affinities inhibitors were never thoroughly explored from biophysical perspective. Here, we present characterizations PKC-ι combination with ICA-1S/1T. Various methods based on light scattering, intrinsic fluorescence, thermal denaturation, heat exchange techniques applied. characteristics, including particle sizing, unfolding, aggregation profiles, enthalpy, entropy, free energy changes, affinity (Kd) presence observed. indicate domain-specific stabilities protein-ligand complex. results spontaneous reaction entropic gain, resulting possible entropy-driven hydrophobic interaction pocket. Altogether, approaches employed this research reveal important insights into interactions