# Targeting fungal ceramide synthases as new antifungals

> **NIH NIH R41** · MICRORID TECHNOLOGIES, INC. · 2024 · $300,000

## Abstract

ABSTRACT
The goal of this project is to discover and develop a new therapeutic(s) more potent than current antifungals for the
treatment of invasive fungal infections. Among invasive fungal infections, cryptococcosis, candidiasis, and aspergillosis
are the most life-threatening.1-3 The incidence of these infections has risen more than 14-fold over the last 20 years,4-11
with a mortality rate of 1,300,000/year.12
We recently discovered a fungal enzyme, ceramide synthase 1 (Cer1), essential for fungal growth at neutral, alkaline
and acidic environments. Thus, a fungal mutant lacking Cer1 is not pathogenic in animal models because, upon
infection, it cannot survive in host neutral (lung and other organs), alkaline (blood) and acidic (inflammatory tissue)
environments.
Thus, Cer1 is an ideal target for the development of new antifungals because any compound blocking Cer1 will be
fungicidal. We have optimized a high throughput assay that allows the screen for inhibitors of ceramide synthase activity
and found few hits that selectively inhibit fungal Cer1. Thus, in this proposal we will continue the screening of the
ChemBridge DIVERSet libraries to select a potent hit molecule(s) that ideally target fungal but not mammalian Ceramide
synthases, to move it forward for medicinal chemistry and preclinical studies. We do have the experience and expertise
to perform these studies.

## Key facts

- **NIH application ID:** 11003526
- **Project number:** 1R41AI186554-01
- **Recipient organization:** MICRORID TECHNOLOGIES, INC.
- **Principal Investigator:** Maurizio Del Poeta
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2024-07-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11003526

## Citation

> US National Institutes of Health, RePORTER application 11003526, Targeting fungal ceramide synthases as new antifungals (1R41AI186554-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11003526. Licensed CC0.

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