# Effective targeting survivin dimerization interface with small molecule inhibitors

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2021 · $345,044

## Abstract

Abstract
 Many proteins have been identified as targets for drug discovery but are considered “undruggable”
because they lack enzymatic activities. This dogma has eliminated many ideal targets and, thus, it has slowed
down progress in fueling discovery of in-vivo chemical probes and potential drugs. Our long-term goal is to
develop new approaches to better target the interaction interface of these “undruggable” proteins. Recently, we
developed a novel concept and an automated computational method to identify interfacial hydrophobic core
residues that serve as nucleation sites to drive protein dimerization. In preliminary studies, we demonstrate
that we have successfully identified and validated a hit compound, LQZ-7, and several active analogues of the
hit with two different chemotypes targeting the critical dimerization core residues in the interface of dimeric
survivin. In this application, we propose to use medicinal chemistry to further optimize these inhibitors and
perform both in-vitro and in-vivo assays to identify lead compounds for further development. To this end, we
will accomplish the following specific aims within the funding period: (1) to chemically modify both chemotypes
for lead identification and optimization; (2) to analyze newly synthesized analogues using biochemical,
biophysical, and cell-based assays; and (3) to determine preclinical pharmacokinetics, toxicity, and in-vivo efficacy
of potential lead compounds. The outcome of this study will not only result in potential new in-vivo chemical
probes and drugs by directly targeting the dimerization domain of survivin, but also provide evidence for a new
approach that can be applied to many other “undruggable” protein dimers in general, which likely will have a
significant and profound impact on future drug discovery process and disease management.

## Key facts

- **NIH application ID:** 9989176
- **Project number:** 5R01GM127656-03
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** Jasmine JingYuan Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,044
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989176

## Citation

> US National Institutes of Health, RePORTER application 9989176, Effective targeting survivin dimerization interface with small molecule inhibitors (5R01GM127656-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989176. Licensed CC0.

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