# Modulate Cullin-RING E3 ubiquitin ligases by small molecule agents

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $702,771

## Abstract

Project Summary
Recently we have discovered a group of drug-like small molecules that inhibit Cullin-RING E3 ubiquitin ligase 4
(CRL4). We have found that these molecules are toxic to a subset of leukemia cell lines, which express very
low levels of the CRL4 component cullin 4. Moreover, the CRL4 inhibitors exhibit anti-tumor activity in
experimental mice. These preliminary findings suggest an interesting possibility that some low-cullin 4-
expressing leukemia lines are vulnerable to our newly discovered CRL4 inhibitors and thus can be exploited for
selective cancer therapies.
In this project, we propose to improve CRL4 inhibitors using synthetic chemistry and to understand the
molecular basis of how the small molecule compounds act to inhibit CRL4. Finally, we will develop both cell-
and animal-based pre-clinical models to evaluate the anti-cancer potential for the CRL4 inhibitors against a
subset of leukemia that are characterized by low cullin 4 abundance. Such information is critical for developing
new strategy to improve the treatment of leukemia.

## Key facts

- **NIH application ID:** 10200718
- **Project number:** 5R01CA251425-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Robert J DeVita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $702,771
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200718

## Citation

> US National Institutes of Health, RePORTER application 10200718, Modulate Cullin-RING E3 ubiquitin ligases by small molecule agents (5R01CA251425-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10200718. Licensed CC0.

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