Cytotoxic Profiling of Korea Chemical Bank Diversity Library

초록

Cytotoxicity profiling of screening libraries is a critical component in early-stage drug discovery to identify compounds with undesirable toxic effects. Here, we report the cytotoxicity profiling of the Korea Chemical Bank (KCB) diversity library, comprising 7040 compounds curated via virtual screening, clustering, and druggability assessment. A subset of 5181 compounds was randomly selected and screened using the WST-1 assay in five mammalian cell lines (HEK293, HFL1, HepG2, NIH3T3, and CHOK1) at concentrations of 30 µM and 10 µM, following 24 h and 48 h incubation periods. Cytotoxic compounds were defined as those exhibiting >50 % inhibition at 30 µM after 48 h. A total of 17 compounds showed consistent cytotoxicity across all five cell lines. Comparative analysis of physicochemical properties revealed that cytotoxic compounds exhibited higher lipophilicity (ALogP/ LogD) and the number of aromatic rings (AR) relative to non-cytotoxic compounds. These results indicate that the majority of the KCB diversity library comprises non-cytotoxic compounds, reflecting effective pre-filtering of toxic physicochemical properties during library design.

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