# Ess1: A pathogenic fungal target for a novel class of broad-spectrum therapeutic agents

> **NIH NIH R43** · KATHERA BIOSCIENCE INC. · 2021 · $298,530

## Abstract

Project Summary
There is a world-wide need for improved treatment of systemic, life-threatening fungal
infections. Current therapies are limited by the small number of approved drugs, toxicities, drug-
drug interactions, mode of administration, and growing problems of drug resistance and
emerging pathogens. Treatment also suffers from a lack of rapid clinical diagnoses, leading to
dependence on broad-spectrum antifungal drugs. Moreover, existing antifungal drug classes
target membrane and cell wall integrity, and there is a need to develop drugs against targets
with new modes of action. Available evidence suggest Ess1 might be one such target. Ess1 is
an essential prolyl isomerase that is highly conserved in fungal pathogens, including Candida
albicans and Aspergillus fumigatus, and its mechanism-of-action is complementary in that it
does not overlap with targets of existing antifungals. Several small molecule "hits" that show
chemical-genetic interactions with Ess1 mutant cells have been identified, and fungal Ess1
structure differs sufficiently from its human ortholog (Pin1) to suggest that development of
selective Ess1 inhibitors is feasible. The specific aims of this Phase I proposal are to (1)
validate Ess1 as a druggable target and (2) identify inhibitor scaffolds that are chemically
tractable for a "hit to lead" drug development program. The approach will use biochemical and
whole-cell assays to test inhibitors against Ess1 and Pin1 enzymes, fungal pathogens, and
mammalian cells, and to develop a robust exploratory chemistry program to accomplish these
aims. The outcomes will advance this program into hit-to-lead, lead optimization and pre-clinical
studies (Phase II). The long-term objective is to develop Ess1 inhibitors into a new class of
broad-spectrum antifungal drugs.

## Key facts

- **NIH application ID:** 10324971
- **Project number:** 1R43AI162468-01A1
- **Recipient organization:** KATHERA BIOSCIENCE INC.
- **Principal Investigator:** Stephen Parent
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $298,530
- **Award type:** 1
- **Project period:** 2021-06-17 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324971

## Citation

> US National Institutes of Health, RePORTER application 10324971, Ess1: A pathogenic fungal target for a novel class of broad-spectrum therapeutic agents (1R43AI162468-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10324971. Licensed CC0.

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