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Updated: Aug 15, 2025
Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
Published on: November 11, 2016
Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map
Shuang Zhang1, Nicholas Lyons2, Marijke Koedam1
1Laboratory for Calcium and Bone Metabolism, Department of Internal Medicine, Erasmus MC, Erasmus University Medical Center, Rotterdam, Netherlands.
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.
Insights
This study identifies emetine and kinetin-riboside as potential drugs to inhibit bone marrow adipogenesis, a process linked to aging and obesity. The research utilized a computational approach combined with experimental validation for drug repurposing.
Area of Science:
- Biomedical Science
- Pharmacology
- Molecular Biology
Background:
- Increased bone marrow adipogenesis is linked to aging, obesity, diabetes, and anorexia nervosa.
- Current treatments for aberrant adipocyte accumulation are limited by drug discovery challenges, including cost and efficacy.
- Drug repurposing offers a cost-effective strategy to identify existing medications for new therapeutic uses.
Purpose of the Study:
- To develop and validate a method for identifying repurposable drugs that inhibit adipogenesis using computational and experimental approaches.
- To screen for small molecules that can counteract the accumulation of bone marrow adipocytes.
Main Methods:
- Utilized the Connectivity Map (CMap) database to prioritize small molecules based on adipocyte-specific gene expression.
- Generated transcriptomic profiles of human mesenchymal stromal cells undergoing adipogenic differentiation.
- Treated cells with prioritized compounds and analyzed their effects on adipogenesis.
Main Results:
- Identified emetine and kinetin-riboside as compounds with potent inhibitory effects on adipogenesis.
- Demonstrated the efficacy of the computational and experimental drug repurposing strategy.
Conclusions:
- Emetine and kinetin-riboside are promising candidates for inhibiting bone marrow adipogenesis.
- The Connectivity Map-based approach provides a viable proof-of-concept for discovering repurposable drugs against aberrant adipogenesis.
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