Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics
About This Grant
Project Summary/Abstract Circadian rhythms are ~24-hour endogenous cycles observed across diverse biological processes. Altered circadian rhythms have been shown to be associated with various diseases, including cancer. Accumulating evidence has demonstrated that the core circadian components, particularly Brain and Muscle ARNT-Like Protein 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), play important roles in different types of cancer, such as glioblastoma (GBM), acute myeloid leukemia (AML), and hepatocellular carcinoma (HCC). These discoveries underline circadian clocks as a promising novel target for cancer treatment. Currently, however, effective BMAL1- and CLOCK-specific chemical probes are still lacking, which prevents the development of novel cancer therapies that directly target the central clock. To discover small-molecule compounds that can specifically modulate BMAL1:CLOCK and have anti-cancer efficacy, we introduced a new strategy by targeting BMAL1:CLOCK in the context of a holoprotein complex that reflects their native conformation. We developed and validated a new drug discovery pipeline that consists of an affinity selection mass spectrometry (AS-MS) based binding assay combined with a series of cell-based HiBiT reporter assays that can assess the endogenous protein properties and dynamics for hit validation. We have implemented this new pipeline in a small-scale pilot screen and identified two small molecules that selectively target BMAL1 and CLOCK, respectively. In this proposal, we aim to implement our new platform in a large-scale high-throughput screening (HTS) campaign, followed by rigorous hit validation. Meanwhile, we will integrate advanced cheminformatics analysis and medicinal chemistry inspection to prioritize the hit set, as a prelude to understanding structure-activity relationships, and optimization of chosen leads. The success of this project will discover more potent compounds for BMAL1 and CLOCK, which will open the door for novel cancer drug development by targeting the circadian system.
Grant Summary
Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics is a NCI - National Cancer Institute grant providing up to $680K for university, nonprofit, healthcare org. Applications are due 2029-05-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $680K
2029-05-31
- 1Confirm your organization is eligible for Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics: Frequently Asked Questions
Who is eligible for the Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics?
Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics provide?
Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics provides up to $680K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics deadline?
Applications for Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics are due 2029-05-31 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics?
To apply for Discovery of novel small molecules targeting a circadian regulatory complex for cancer therapeutics, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.