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Updated: May 31, 2025
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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
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Multi-Omics and Network-Based Drug Repurposing for Septic Cardiomyopathy.
Pei-Pei Liu1, Xin-Yue Yu2, Qing-Qing Pan3
1Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Pharmaceuticals (Basel, Switzerland)
|January 25, 2025
Summary
This study identified acetaminophen and pyridoxal phosphate as potential treatments for septic cardiomyopathy (SCM). These drugs improved cardiac function in mice and offer hope for patients with sepsis-induced heart complications.
Area of Science:
- Cardiovascular Research
- Sepsis Pathophysiology
- Drug Discovery
Background:
- Septic cardiomyopathy (SCM) is a serious cardiac complication of sepsis with limited treatment options.
- Effective therapeutic strategies for SCM are urgently needed.
Purpose of the Study:
- To identify repurposable drugs for septic cardiomyopathy using integrated multi-omics and network analyses.
- To evaluate the efficacy and mechanisms of candidate drugs in preclinical models.
Main Methods:
- Generated a lipopolysaccharide (LPS)-induced mouse model of septic cardiomyopathy.
- Utilized ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and RNA sequencing (RNA-seq) for multi-omics data generation.
- Employed network proximity analysis to screen for FDA-approved drugs and validated top candidates in vivo and in vitro.
Main Results:
- Network analysis identified 129 potential drugs, refined to 14 candidates.
- Acetaminophen and pyridoxal phosphate significantly improved cardiac function (ejection fraction, fractional shortening) and reduced cardiac injury biomarkers (BNP, cTn-I) in SCM mice.
- Acetaminophen demonstrated anti-inflammatory effects by inhibiting prostaglandin synthesis, while pyridoxal phosphate supported cellular function by restoring amino acid balance.
Conclusions:
- This study establishes a robust platform for drug repurposing in SCM.
- Acetaminophen and pyridoxal phosphate are identified as promising candidates for clinical translation in septic patients with cardiac complications.
