# Mechanism and Inhibition of Protein Arginine Methylation

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $300,444

## Abstract

Protein arginine methylation, which is specifically mediated by protein arginine methyltransferases (PRMTs),
represents one of the most important and ubiquitous posttranslational modifications in biological regulation.
PRMTs are involved in a variety of cellular processes including epigenetic reprograming, RNA splicing,
signal transduction, and DNA repair. Significant amounts of evidence have shown that altered PRMT
expression and activity are associated with tumorigenesis, inflammation, diabetes, neurological disorders,
and many other recalcitrant disease conditions. PRMTs are highly promising molecular targets in the search
for new chemotherapies. However, functions of PRMT enzymes in regulating signaling cascades and
disease pathways are poorly understood. Molecular mechanisms of PRMTs in major oncology processes
are not yet defined. Importantly, quality chemical leads are scarce for effective targeting of arginine
methylation, which significantly hampers current pharmaceutical advance. This research project is aimed at
developing novel chemical biology strategies and organic probes as powerful mechanistic means to
interrogate PRMT function in key biological pathways and disease processes. We will innovate multiple
lines of strategic designs to determine substrate recognition mechanisms of PRMTs and illuminate
functional interplays among key histone modifications in epigenetic fate regulation. Great efforts will be
engaged in developing potent and subtype-selective small molecule inhibitors with privileged structural
scaffolds that can be used to selectively block the enzymatic activity of the major PRMT subtypes. A
diversity of library compounds will be screened; chemical analogs will be synthesized; and best leads will be
characterized for their pharmacokinetics and pharmacodynamics properties. Detailed biochemical, cellular,
and in vivo studies will be conducted in a systematic way to define structure-activity relationship and
mechanism of action with the goal of generating a new generation of potent, subtype-selective PRMT
inhibitors. Altogether, the projected research will yield in-depth understanding of PRMT-regulated disease
mechanisms and translate laboratory leads into clinical candidates for the treatment of PRMT-related
ailments.

## Key facts

- **NIH application ID:** 9840912
- **Project number:** 5R01GM126154-03
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Y. George Zheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,444
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840912

## Citation

> US National Institutes of Health, RePORTER application 9840912, Mechanism and Inhibition of Protein Arginine Methylation (5R01GM126154-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9840912. Licensed CC0.

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