Anti-proliferative Profiling of 6,000 Representative Compounds from the Korean Chemical Bank Diversified Compound Library in De-differentiated Schwann Cells

Early effective in vitro profiling using a vast collection of compounds is crucial to identify hits from large-scale drug screening to find novel therapeutic targets. The usage of molecules with distinct structural properties enhances the possibility of finding fascinating leads and compounds with various biological functions. This study aimed to find effective structures for inhibiting the proliferation of de-differentiated Schwann cells. In this study, we investigated the anti-proliferative effect of 6,000 novel compounds from the Korean Chemical Bank Diversified Compound Library (KCB-DCL) against in vitro de-differentiated Schwann cells at a single dose concentration of 30 μM. Their physiochemical properties, as well as hit rates, molecular targets associated with Schwann cell proliferation, such as proto-oncogene tyrosine-protein kinase Src (SRC), and docking of the selected leads, were assessed. We identified 1,420 hits (23.66%) with an impact on cell viability among 6,000 novel diversified compounds. Ten potential leads (a-j) were chosen from the hits and subjected to docking analysis. Compound e showed the best selectivity toward SRC and had a greater binding affinity (- 10.7 kcal/mol) than the well-known SRC inhibitor dasatinib (- 7.5 Kcal/mol). These results can provide a foundation for the early stages of drug discovery for the development of novel modulators aimed at SRC receptor proteins in Schwann cells to treat peripheral neurodegenerative diseases.