Exploration of small molecule compounds targeting abdominal aortic aneurysm based on CMap database and molecular...

Area of Science:

• Vascular Biology
• Pharmacology
• Bioinformatics

Background:

• Abdominal aortic aneurysm (AAA) growth poses significant rupture risks, necessitating new pharmaceutical treatments.
• Current therapeutic options for AAA are limited, driving the search for novel drug candidates.

Purpose of the Study:

• To identify potential pharmaceutical interventions for mitigating abdominal aortic aneurysm (AAA) growth.
• To explore novel therapeutic agents for AAA treatment by analyzing transcriptome data and predicting drug-target interactions.

Main Methods:

• Differential gene expression analysis of AAA transcriptome data.
• Bioinformatic prediction of small molecules and their targets using the Connectivity Map (CMap).
• Molecular docking, dynamics simulations, and CETSA experiments to validate drug-target binding and stability.

Main Results:

• Identified 2244 differentially expressed genes (DEGs) in AAA, enriched in tubulin binding and cell cycle pathways.
• Apicidin emerged as a potential therapeutic agent targeting HDAC4, with strong predicted binding affinity (-8.218 kcal/mol) and stable complex formation.
• CETSA experiments confirmed Apicidin's ability to bind HDAC4 within cells.

Conclusions:

• Apicidin effectively inhibits HDAC4 in the context of abdominal aortic aneurysm (AAA).
• The drug exhibits favorable protein-ligand interactions and complex stability, positioning it as a promising candidate for AAA pharmacotherapy.