# Discovery of next-generation dengue NS4B inhibitors

> **NIH NIH U19** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $2,384,773

## Abstract

PROJECT 5 – ABSTRACT
The goal of this project is to discover next-generation dengue NS4B inhibitors. We currently have a pan-dengue
serotype NS4B inhibitor NITD-688 in phase I clinical trial. Preclinical results suggest two potential liabilities that
might threaten this compound for further development. Thus, we will develop a second-generation compound to
mitigate the liabilities. We will achieve the goal by pursuing three aims. (i) Optimize the next generation of dengue
NS4B inhibitor. We have developed a comprehensive medicinal chemistry optimization strategy to improve the
compound properties. (ii) Conduct preclinical characterization and deliver an IND-ready next-generation NS4B
inhibitor. (iii) Determine the mode-of-action and resistance potential of NITD-688. NS4B is a transmembrane
protein that participates in replication complex through interacting with other viral and host proteins. We will take
chemo-proteomic, biochemical, and cellular approaches to define the mechanism of compound inhibition. Such
knowledge can be applied to other membrane proteins for antiviral discovery.

## Key facts

- **NIH application ID:** 10514156
- **Project number:** 1U19AI171413-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Christopher Sarko
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,384,773
- **Award type:** 1
- **Project period:** 2022-05-16 → 2025-03-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514156

## Citation

> US National Institutes of Health, RePORTER application 10514156, Discovery of next-generation dengue NS4B inhibitors (1U19AI171413-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10514156. Licensed CC0.

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