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

Mohammad Ashrafuddin Khan; Lee Seyeon (이세연); HUH YOUNG BUHM (허영범); KIM JA-EUN (김자은); Kyo Seon Hwang; LEE JI HYUN (이지현); Hwajin Lee (이화진); Yoo Lim Chun (천유림); JUNG NA YOUNG (정나영); Jung Junyang (정준양)

doi:10.11637/aba.2023.36.3.103

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

Anatomy & Biological Anthropology
Abbr : Anat Biol Anthropol
2023, 36(3), pp.103~110
DOI : 10.11637/aba.2023.36.3.103
Publisher : 대한체질인류학회
Research Area : Medicine and Pharmacy > Anatomy
Received : June 29, 2023
Accepted : August 31, 2023
Published : September 30, 2023

Mohammad Ashrafuddin Khan ¹, Lee Seyeon ¹, HUH YOUNG BUHM ¹, KIM JA-EUN ¹, Kyo Seon Hwang ², LEE JI HYUN ¹, Hwajin Lee ¹, Yoo Lim Chun ¹, JUNG NA YOUNG ³, Jung Junyang ¹

¹경희대학교
²Kyung Hee University
³동아대학교

Accredited

ABSTRACT

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.

KEYWORDS

Korean Chemical Bank Diversified Compound Library (KCB-DCL), Anti-proliferative, Schwann cells, Peripheral nerve degeneration, SRC

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* References for papers published after 2023 are currently being built.

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This paper was written with support from the National Research Foundation of Korea.

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Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

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

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* References for papers published after 2023 are currently being built.

Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

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

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