# Pharmacological targeting of circadian clock components to treat glioblastoma

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2021 · $475,000

## Abstract

Project Summary.
This request for an administrative supplement is submitted in response to NOT-AG-20-034, Alzheimer' s-focused
administrative supplements for NIH grants that are not focused on Alzheimer's disease. Disruption of circadian
rhythm and sleep, long considered to be a symptom of Alzheimer's Disease and related dementia (ADRD), is
increasingly recognized as an early contributor to disease onset and progression. This may be explained by the
role of the circadian clock in maintaining the homeostatic function of the brain. At the molecular level, circadian
clock components are linked to transcriptional regulation of genes implicated in the homeostatic regulation of
energy balance, reactive oxygen species production, neuroinflammation, proteostasis, protein secretion,
synaptic function, housekeeping functions of neurons, astrocytes, and glia. Age-related dampening of the
circadian clock may increase the risk for ADRD. Conversely, behavioral or pharmacological approaches to boost
circadian rhythm or function of clock components are novel strategies to manage ADRD.
Our research team has provided the first proof-of-concept of using the first-generation pharmacological tool
targeting the circadian clock components REV-ERB alpha and beta (NR1D1 and NR1D2) in a mouse model of
ADRD. Daily administration of the REV-ERB agonist SR9009 effectively reduced the disease severity as
evidenced by improvement in behavioral tests and reduction in a aggregates. However, there are major
knowledge gaps- the molecular mode of action of this first-generation drug on the AD mouse model is unknown,
and there is an urgent need to develop the next generation REV-ERB agonists with improved pharmacological
characteristics and potency. This supplemental fund requested will be used to (a) characterize the mode of action
of SR9009 in the brain of mouse AD model and (b) screen novel REV-ERB agonists for improved efficacy in cell-
based assays. Completion of the proposed experiments will offer new insight into the mode of action of REV-
ERB compounds in alleviating the disease severity of ADRD and the discovery of new chemical entities with
improved pharmacological properties in neurons. These critical results obtained with the supplemental budget
will form the foundation for future research to develop novel compounds targeting the circadian clock to treat
ADRD.

## Key facts

- **NIH application ID:** 10289686
- **Project number:** 3R01CA236352-03S1
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Satchidananda Panda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $475,000
- **Award type:** 3
- **Project period:** 2019-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10289686

## Citation

> US National Institutes of Health, RePORTER application 10289686, Pharmacological targeting of circadian clock components to treat glioblastoma (3R01CA236352-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10289686. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*