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

Frontiers in endocrinology
Authors
Keywords
Abstract

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.

Year of Publication
2022
Journal
Frontiers in endocrinology
Volume
13
Pages
1017832
Date Published
12/2022
ISSN
1664-2392
DOI
10.3389/fendo.2022.1017832
PubMed ID
36589834
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