# Structure-based characterization of CtBP as a therapeutic target in cancer

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $317,240

## Abstract

C-terminal Binding Proteins (CtBP) 1 and 2 operate as transcriptional coregulators that
modulate numerous cellular processes including repressing genes involved in genome stability,
epithelial differentiation and apoptosis. Substantial evidence implicates CtBP in multiple human
cancers. CtBP contains a functional enzymatic domain, providing substrate, coenzyme and
adjacent pockets, which is both highly unusual among transcription factors and potentially
valuable for inhibitor design. Our crystallographic analysis of CtBP1 and CtBP2 has revealed
unique details of the active site that we have already used in structure based drug design to
develop the highest affinity CtBP inhibitor identified to date. We have assembled an
interdisciplinary team with strengths structural biology, structure based drug design, cancer
biology and medicinal chemistry to extend these studies. Our project will use computational
analysis of the binding sites to identify potential inhibitors; those identified will be screened by
enzymatic and biophysical techniques to determine binding affinity and crystallographic analysis
to determine the stereochemistry of binding. These results will inform novel chemical synthesis
to develop additional inhibitors. We will also investigate the role of oligomerization and catalysis
in CtBP transcriptional function to inform additional inhibitor design and synthesis studies.
These studies are directed at understanding CtBP structure and function at a level that will lead
to inhibitors that can serve as important molecular probes in the study of CtBP in cancer and,
eventually, to the development of highly selective anti-neoplastic CtBP inhibitors.

## Key facts

- **NIH application ID:** 9849301
- **Project number:** 5R01GM119014-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** WILLIAM E ROYER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,240
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849301

## Citation

> US National Institutes of Health, RePORTER application 9849301, Structure-based characterization of CtBP as a therapeutic target in cancer (5R01GM119014-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849301. Licensed CC0.

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