# Robust rational design of chemical tools to inhibit RNA-binding proteins

> **NIH NIH R01** · RESEARCH INST OF FOX CHASE CAN CTR · 2020 · $357,960

## Abstract

Abstract
 RNA-binding proteins (RBPs) regulate the life cycle of target mRNAs by controlling splicing,
polyadenylation, stability, localization and translation, and they also modulate function of non-coding RNAs.
Because of their crucial roles in many diverse cellular processes, RBPs are key targets for therapeutic
intervention in a variety of human diseases ranging from cancers to neurodegeneration.
 We have recently developed a new and unique computational approach for designing inhibitors of a
given RBP, starting from its structure in complex with RNA. We have validated this approach by applying it to
three separate RBPs, and in each case we have identified inhibitors of our target proteins. Nonetheless, there
is room for further improvement in the compounds we identify using this method. Here, we propose to extend
this computational approach, to improve the initial hit compounds’ potency, selectivity, and diversity. With these
enhancements in place, this approach will provide new chemical tools to explore the biology of individual RBPs
at unprecedented detail. To facilitate rapid and broad adoption of this method, we will also make the
computational tools accessible through a webserver, so that the community of researchers wishing to design
inhibitors for their own RBPs of interest will be able to easily use them.
 This research is expected to have an important positive impact because it will provide new insights and
tools to address the distinct challenges associated with finding small-molecule inhibitors of protein-RNA
interactions. This contribution is significant because a broad assortment of human diseases stem from
disregulation of protein-RNA interactions, positioning such inhibitors as potential starting points for developing
a variety of new therapeutic agents.

## Key facts

- **NIH application ID:** 9978889
- **Project number:** 5R01GM123336-04
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** John Karanicolas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,960
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978889

## Citation

> US National Institutes of Health, RePORTER application 9978889, Robust rational design of chemical tools to inhibit RNA-binding proteins (5R01GM123336-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978889. Licensed CC0.

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