# Targeting epigenetic reader GAS41

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $504,038

## Abstract

Abstract
Post-translational modifications on histone proteins play an essential role in regulating chromatin transcription
in human cancers. Histone acetylation is associated with active gene transcription and plays a crucial role in
tumorigenesis. Indeed, small molecules targeting proteins involved in regulation of histone modifications are
being explored as a very promising anti-cancer agents, with a number of compounds currently in clinical trials
(e.g. BRD4 inhibitors). Recently, the YEATS domains have been discovered as novel acetyl-histone reader
domains. GAS41 was originally found to be amplified in 23% glioblastomas and 80% astrocytoma. Emerging
studies strongly implicate GAS41 as an oncogene in Non-Small Cell Lung Cancer (NSCLC). GAS41 is
frequently amplified in NSCLC and knockdown of GAS41 or disruption of the interaction with acetylated
histones suppresses lung cancer cell growth.
We have recently found that GAS41 is a reader of di-acetylated H3 histone. Full-length GAS41 is dimeric in
cells and binds di-acetylated H3 with high affinity. Based on this finding we developed suites of biochemical
assays suitable for characterization of GAS41 protein-protein interactions and identification of small molecule
inhibitors. In this proposal we plan to develop small molecule inhibitors of GAS41 using high throughput
screening (HTS) in CCG at the University of Michigan. Small molecule inhibitors of GAS41 will be validated
and characterized in a series of biochemical and biophysical experiments. Activity of the most potent
compounds will be characterized in cell-based assays to assess the disruption of GAS41 interactions with
chromatin and understand mechanism of action. Selected GAS41 inhibitors will be also profiled in a panel of
lung cancer cell lines. In summary, we expect to identify highly valuable chemical probe compounds targeting
GAS41 protein-protein interactions suitable for mechanistic studies and pave the way towards development of
potent in vivo active GAS41 inhibitors.

## Key facts

- **NIH application ID:** 10115000
- **Project number:** 5R01CA240514-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Tomasz Cierpicki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $504,038
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115000

## Citation

> US National Institutes of Health, RePORTER application 10115000, Targeting epigenetic reader GAS41 (5R01CA240514-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10115000. Licensed CC0.

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