Related Experiment Video
Updated: Jan 22, 2026
05:10
Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
Published on: December 11, 2016
10.2K
Repurposing the thrombopoietin receptor agonist eltrombopag as an anticryptococcal agent
Hao-Tai Ko1,2, Li-Hang Hsu1, Sheng-Yung Yang1
1Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617 Taiwan.
Medical Mycology
|July 13, 2019
Summary
Eltrombopag, an FDA-approved drug, shows potent antifungal activity against Cryptococcus species by disrupting virulence factors. This repurposed drug may offer a new treatment for cryptococcosis.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Cryptococcosis is a serious fungal infection, particularly in immunocompromised individuals.
- Existing antifungal treatments face challenges like resistance and toxicity.
- Repurposing FDA-approved drugs offers a faster route to new therapeutic options.
Purpose of the Study:
- To investigate the anticryptococcal potential of FDA-approved drugs.
- To evaluate eltrombopag, a drug with novel antifungal activity, as a treatment for cryptococcosis.
Main Methods:
- Screened 1018 FDA-approved drugs against Cryptococcus neoformans.
- Determined minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) for eltrombopag.
- Assessed eltrombopag's synergy with other drugs using fractional inhibitory concentration index (FICI).
- Investigated eltrombopag's impact on cryptococcal virulence factors and associated genes via RNA sequencing.
Main Results:
- Eltrombopag demonstrated antifungal activity against Cryptococcus neoformans/gattii, Candida glabrata, and Trichophyton rubrum.
- Eltrombopag inhibited key cryptococcal virulence factors, including capsule and biofilm formation, and melanin production.
- RNA sequencing identified genes in the calcineurin pathway, lipid biosynthesis, and membrane transport associated with eltrombopag's action.
- Eltrombopag exhibited synergistic effects with FK506, a calcineurin inhibitor.
Conclusions:
- Eltrombopag possesses significant antifungal activity against Cryptococcus species.
- Its mechanism involves interfering with virulence factors and the calcineurin pathway.
- Eltrombopag shows promise for repurposing as an effective antifungal agent for cryptococcosis treatment.
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