# Tandem Discovery of Drug Leads and Targets via Paal-Knorr reaction

> **NIH NIH R21** · TEXAS STATE UNIVERSITY · 2020 · $162,125

## Abstract

7. Project Summary
The process of drug design currently begins with a drug lead and/or target. It involves the refinement of that lead
and target combination to achieve optimal specificity for high efficacy and reduced off-target effects. The
proposed exploratory technology development program focuses on the discovery of a new platform for drug
design that identifies both lead and target in parallel. It combines the recently emerged ‘protein-templated
fragment ligation (PTFL)’ concept with underexplored Paal-Knorr chemistry. For the purpose of technology
development, we have centered our efforts on the identification of new leads and targets for pain. This model
provides an ideal arena for technology development since opioid misuse in the United States has attained
epidemic proportions while targeting established proteins such as COX-2 has reached a threshold generating
an emergent need to rapidly discover and explore alternative targets. As the first Specific Aim, we will
demonstrate the use of the proposed platform by employing the Paal-Knorr reaction to deliver novel COX-2
pyrrole-containing probes, hits and leads. As many targets cannot be expressed and used in vitro, we will then
focus on translating the platform to operate in mammalian cells. As the second Specific Aim, we will demonstrate
how our method can be used to identify probes to unexplored targets. While developed for the discovery of new
leads for pain, the proposed approach is general in nature and can be applied for therapeutic discovery for a
wide range of ailments including but not limited to cancer, neurodegenerative diseases, stroke, and infectious
disease. If successful, this technology and expansions thereon could add an important next-generation tool to
further revolutionize the drug discovery process.

## Key facts

- **NIH application ID:** 10004127
- **Project number:** 5R21GM131717-02
- **Recipient organization:** TEXAS STATE UNIVERSITY
- **Principal Investigator:** ALEXANDER KORNIENKO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $162,125
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004127

## Citation

> US National Institutes of Health, RePORTER application 10004127, Tandem Discovery of Drug Leads and Targets via Paal-Knorr reaction (5R21GM131717-02). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10004127. Licensed CC0.

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