# Pharmacological targeting of circadian clock components to treat glioblastoma

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2022 · $421,184

## Abstract

The circadian clock regulates physiologic processes by establishing cyclical rhythms.
Circadian clock genes control key pathways altered during tumorigenesis including metabolism, inflammation,
cell cycle, autophagy and DNA damage responses. Importantly, disruption of circadian rhythms increases
cancer risk, and several physiologically oscillating pathways lose their rhythmic activity in cancer. These
observations suggest that pharmacological modulation of the circadian clock machinery can be targeted for
cancer treatment. However, the link between pharmacological intervention of the circadian clock and new
therapeutic strategies for cancer prevention and treatment has yet to be demonstrated. This project provided a
first-proof of concept using a pre-clinical animal model of glioblastoma by deploying the first-generation
chemical tools SR9009 and SR9011 targeting nuclear receptor (NR) subfamily 1 group D member 1 (NR1D1)
and NR1D2 (REV-ERSs). Although these small molecules were more effective than the standard of care drug
for glioblastoma treatment, this first generation of NR ligands have relatively poor pharmacological
characteristics limiting potency and general applicability for patient disease treatment. Therefore, the lab
proposes to optimize REV-ERB agonists and validate their anticancer activity towards glioblastomas in vitro
and pre-clinically in vivo alone or in combination with established clinical modalities to support translation of
lead molecules for treating devastating diseases with limited therapeutic treatments.

## Key facts

- **NIH application ID:** 10470347
- **Project number:** 5R01CA236352-04
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Satchidananda Panda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $421,184
- **Award type:** 5
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470347

## Citation

> US National Institutes of Health, RePORTER application 10470347, Pharmacological targeting of circadian clock components to treat glioblastoma (5R01CA236352-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10470347. Licensed CC0.

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