# Discovery of Thymidylate Kinase Inhibitors for Anti-Fungal Applications

> **NIH NIH R21** · CARNEGIE-MELLON UNIVERSITY · 2022 · $195,975

## Abstract

Discovery of Thymidylate Kinase Inhibitors for Anti-Fungal Applications
Abstract:
Infections due to the fungal pathogen Candida albicans are devastating to the human population. C.
albicans causes over 40,000 cases of invasive candidiasis/year in the US alone, with an estimated mortality
rate of approximately 20%. There are only a small number of approved anti-fungal agents and resistance to
these drugs is becoming common. We propose to isolate and characterize inhibitors of thymidylate kinase
that can be developed as anti-fungal drugs. Thymidylate kinase catalyzes the phosphorylation of thymidine
monophosphate to diphosphate, and it is an essential step in the production of TTP, which is required for
DNA replication and repair. We propose to use high-throughput screening (HTS) of compound libraries,
computational drug discovery, and Nuclear magnetic resonance (NMR) based screening of fragment
libraries, to identify lead compounds. The proposal leverages expertise in thymidylate kinase enzymology
and NMR (Rule), HTS (Johnston), computational chemistry (Isayev), and C. albicans biology (Mitchell).

## Key facts

- **NIH application ID:** 10453065
- **Project number:** 1R21AI167017-01A1
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** GORDON S. RULE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,975
- **Award type:** 1
- **Project period:** 2022-01-18 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453065

## Citation

> US National Institutes of Health, RePORTER application 10453065, Discovery of Thymidylate Kinase Inhibitors for Anti-Fungal Applications (1R21AI167017-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10453065. Licensed CC0.

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