Assay development and screening for discovery of chemical probes, drugs or immunomodulators (R01 Clinical Trial Not Allowed)

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Description

This funding opportunity from the National Cancer Institute (NCI), part of NIH, aims to stimulate discovery and development of novel small molecules relevant to cancer biology. The molecules may serve as chemical probes to elucidate biological mechanisms or as potential therapeutic or immunomodulatory agents targeting tumor cells or immune cells involved in tumor regulation.

The research supported under this Notice of Funding Opportunity (NOFO) covers three main stages:

1. Assay Development and Pilot Screening: Design and validation of primary screening assays targeting specific biological targets, pathways, or phenotypes relevant to cancer. Assays should be innovative and may include biochemical, cellular, or organism-based approaches. Pilot screening with small compound libraries (e.g., LOPAC1280) is encouraged to validate assay performance.

2. Primary Screen Implementation: Execution of high-throughput or moderate-throughput screening to identify initial hits. This may include virtual screening approaches using computational methods such as machine learning-based QSAR, protein-ligand docking, similarity searches, or pharmacophore mapping. Collaboration with experienced screening facilities is recommended.

3. Hit Validation: Secondary and orthogonal assays to confirm activity, eliminate false positives, and characterize mode of action. This includes cheminformatics analysis, medicinal chemistry inspection to prioritize hits, and testing of powder samples and analogs. In vivo assays are only appropriate if justified for biological effect demonstration.

The NOFO emphasizes rigorous target validation, assay reproducibility, and careful hit validation to improve the success rate of small molecule discovery. Projects focusing on rare or neglected cancers, pediatric fusion oncoproteins, small cell lung cancer, or pancreatic cancer are encouraged.

Applications may propose work in one or more of these stages but must provide strong justification and preliminary data for multi-stage projects. Clinical trials are explicitly not allowed under this FOA.

Due Dates

• October 5, 2023
• February 5, 2024
• June 5, 2024
• October 5, 2024
• February 5, 2025
• June 5, 2025
• October 5, 2025
• February 5, 2026
• June 5, 2026

All applications are due by 5:00 PM local time of the applicant organization. Applicants are encouraged to submit early to allow time for corrections.

Funding Amount

• Application budgets are not limited but must reflect the actual needs of the proposed project.
• Project period may not exceed 3 years.
• Number of awards depends on NIH appropriations and meritorious applications.

Eligibility

Eligible applicants include:

• Public and private institutions of higher education (including HBCUs, Hispanic-serving institutions, tribal colleges, etc.)
• Nonprofits with or without 501(c)(3) status (excluding institutions of higher education)
• For-profit organizations including small businesses
• State, county, city, and special district governments
• Federally recognized and other Native American tribal governments and organizations
• Independent school districts, public housing authorities
• Foreign institutions and foreign components of U.S. organizations are eligible
• Others as specified in the full FOA

Applicants must complete all required registrations (SAM, eRA Commons, Grants.gov) prior to submission.

Application Process

• Applications must be submitted electronically via Grants.gov and tracked in eRA Commons.
• Follow the SF424 (R&R) Application Guide and program-specific instructions in the NOFO.
• Letter of Intent is encouraged but not required, due 30 days prior to application deadline.
• Applications must include a detailed Research Strategy addressing Significance, Innovation, and Approach, with preliminary data supporting the proposed scope.
• Include a flow diagram outlining critical steps and timelines for the proposed discovery stage(s).
• Data Management and Sharing Plan is required and should include willingness to deposit screening data and protocols to PubChem.
• Limited appendix materials allowed per NIH guidelines.
• Applications requesting $500,000 or more in direct costs in any year must contact NIH staff 6 weeks prior to submission.

Review Criteria

Applications will be evaluated on:

• Significance: Importance of the target and potential impact on cancer biology and therapy.
• Investigator(s): Expertise and experience relevant to the proposed research.
• Innovation: Novelty of the target, assay design, and screening approach.
• Approach: Scientific rigor, feasibility, preliminary data, and plans for assay development, screening, and hit validation.
• Environment: Institutional support and resources.

Additional considerations include protections for human subjects, inclusion of diverse populations, vertebrate animal use, biohazards, and resource sharing plans.

Additional Information

• Clinical trials are not allowed under this FOA.
• Applications proposing non-cancer targets or detailed SAR studies are non-responsive.
• In vivo animal studies are only allowed if justified for hit validation.
• Applicants are encouraged to use resources such as the NCI Developmental Therapeutics Program and public compound libraries.
• Data generated from this research is expected to be shared publicly via PubChem.

External Links

• Funding Opportunity Announcement (PAR-23-264)
• NCI Developmental Therapeutics Program
• NCI Program for Natural Product Discovery (NPNPD) Prefractionated Library
• Assay Guidance Manual
• PubChem BioAssay Database
• Academic Drug Discovery Consortium
• Chemical Probes Portal
• NIH Grants Policy Statement
• NIH Data Management and Sharing Policy

Contact Information