Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map

Shuang Zhang, Nicholas Lyons, Marijke Koedam, Jeroen van de Peppel, Johannes P T M van Leeuwen, Bram C J van der Eerden*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Several physiological and pathological conditions such as aging, obesity, diabetes, anorexia nervosa are associated with increased adipogenesis in the bone marrow. A lack of effective drugs hinder the improved treatment for aberrant accumulation of bone marrow adipocytes. Given the higher costs, longer duration and sometimes lack of efficacy in drug discovery, computational and experimental strategies have been used to identify previously approved drugs for the treatment of diseases, also known as drug repurposing. Here, we describe the method of small molecule-prioritization by employing adipocyte-specific genes using the connectivity map (CMap). We then generated transcriptomic profiles using human mesenchymal stromal cells under adipogenic differentiation with the treatment of prioritized compounds, and identified emetine and kinetin-riboside to have a potent inhibitory effect on adipogenesis. Overall, we demonstrated a proof-of-concept method to identify repurposable drugs capable of inhibiting adipogenesis, using the Connectivity Map.

Original languageEnglish
Article number1017832
JournalFrontiers in Endocrinology
Publication statusPublished - 16 Dec 2022

Bibliographical note

Funding Information:
SZ is supported by the China Scholarship Council through a Ph.D. Research Fellowship Grant (No. 201709370052).

Publisher Copyright:
Copyright © 2022 Zhang, Lyons, Koedam, van de Peppel, van Leeuwen and van der Eerden.


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