Related Experiment Video
Updated: May 10, 2026
High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
Published on: March 3, 2015
A c-Myc activation sensor-based high-throughput drug screening identifies an antineoplastic effect of nitazoxanide
Hua Fan-Minogue1, Sandhya Bodapati, David Solow-Cordero
1Corresponding Author: Sanjiv S. Gambhir, Molecular Imaging Program at Stanford, Stanford University School of Medicine, 318 Campus Drive, East Wing, 1st Floor, Stanford, CA 94305-5427. sgambhir@stanford.edu.
Abstract:
Deregulation of c-Myc plays a central role in the tumorigenesis of many human cancers. Yet, the development of drugs regulating c-Myc activity has been challenging. To facilitate the identification of c-Myc inhibitors, we developed a molecular imaging sensor-based high-throughput screening (HTS) system. This system uses a cell-based assay to detect c-Myc activation in a HTS format, which is established from a pure clone of a stable breast cancer cell line that constitutively expresses a c-Myc activation sensor. Optimization of the assay performance in the HTS format resulted in uniform and robust signals at the baseline. Using this system, we conducted a quantitative HTS against approximately 5,000 existing bioactive compounds from five different libraries. Thirty-nine potential hits were identified, including currently known c-Myc inhibitors. There are a few among the top potent hits that are not known for anti-c-Myc activity. One of these hits is nitazoxanide, a thiazolide for treating human protozoal infections. Validation of nitazoxanide in different cancer cell lines revealed a high potency for c-Myc inhibition with IC50 ranging between 10 and 500 nmol/L. Oral administration of nitazoxanide in breast cancer xenograft mouse models significantly suppressed tumor growth by inhibition of c-Myc and induction of apoptosis. These findings suggest a potential of nitazoxanide to be repurposed as a new antitumor agent for inhibition of c-Myc-associated neoplasia. Our work also demonstrated the unique advantage of molecular imaging in accelerating discovery of drugs for c-Myc-targeted cancer therapy.
Insights
A new molecular imaging system identified nitazoxanide as a potent inhibitor of c-Myc. This repurposed drug suppressed breast cancer growth in mice, highlighting its potential as an anti-cancer agent targeting c-Myc-driven tumors.
Area of Science:
- Oncology
- Molecular Imaging
- Drug Discovery
Background:
- Deregulation of c-Myc is a key driver in human cancer tumorigenesis.
- Developing drugs to regulate c-Myc activity presents significant challenges.
- Targeting c-Myc is a promising strategy for cancer therapy.
Purpose of the Study:
- To develop a high-throughput screening (HTS) system for identifying c-Myc inhibitors.
- To discover novel compounds with anti-c-Myc activity.
- To evaluate the potential of repurposing existing drugs for c-Myc-targeted cancer therapy.
Main Methods:
- Established a cell-based molecular imaging sensor assay for detecting c-Myc activation in HTS format.
- Screened approximately 5,000 bioactive compounds from diverse libraries.
- Validated identified hits, including nitazoxanide, in cancer cell lines and xenograft models.
Main Results:
- Identified 39 potential c-Myc inhibitors, including known agents and novel compounds.
- Nitazoxanide demonstrated potent c-Myc inhibition (IC50: 10-500 nmol/L) across various cancer cell lines.
- Nitazoxanide significantly suppressed tumor growth in breast cancer xenograft models by inhibiting c-Myc and inducing apoptosis.
Conclusions:
- Nitazoxanide shows significant potential for repurposing as an antitumor agent against c-Myc-associated cancers.
- Molecular imaging HTS systems are effective in accelerating the discovery of targeted cancer therapeutics.
- This study validates nitazoxanide as a promising candidate for c-Myc-targeted cancer therapy.
