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

The National Cancer Institute (NCI) is issuing a Notice of Funding Opportunity (NOFO) titled "Assay Development and Screening for Discovery of Chemical Probes, Drugs, or Immunomodulators" (PAR-25-153), under the R01 Research Project Grant mechanism. This funding aims to support research for discovering and developing small molecules that advance knowledge in cancer biology by serving as chemical probes or as foundations for new cancer therapies. The NOFO focuses on three stages of discovery research: 1) development and initial pilot testing of primary screen assays, 2) implementation of primary screening to identify potential hits, and 3) validation of hits using secondary assays and initial medicinal chemistry. The NOFO does not support clinical trials and specifically seeks to encourage basic research stages in drug discovery. Projects submitted under this NOFO should prioritize targets relevant to cancer biology and treatment strategies, including small molecules aimed at cancer cells, immune checkpoints, or novel cancer pathways, such as those in pediatric fusion oncoproteins or cancers like small cell lung and pancreatic cancers. The NOFO supports assay development across a range of methodologies, from target-based biochemical assays to phenotypic screening approaches, with flexibility in the selection of the screen type, provided relevance to cancer treatment or biology is demonstrated. Virtual screening approaches may also be considered but should be paired with experimental hit validation and collaboration with cheminformatics and medicinal chemistry experts. Application budgets are not capped, although they should accurately reflect project needs, with a maximum project period of three years. Applications should align with the discovery stages and provide preliminary data to substantiate project feasibility. For instance, proposals that include high-throughput screening (HTS) should provide data showing assay robustness, including reproducibility metrics and sensitivity for weak binding compounds. For hit validation stages, applications should include a clear hit validation scheme and a critical path diagram, outlining timelines and benchmarks. Eligibility for this funding is broad, including higher education institutions, nonprofits, for-profit entities, government organizations, and some foreign entities. Registration in SAM, Grants.gov, and eRA Commons is required. Multiple applications from a single institution are allowed if they are scientifically distinct. Review criteria include the significance of the proposed research, especially the novelty and relevance of the target in cancer treatment, and the rigor and feasibility of the approach, with specific requirements for assay development, screening, and hit validation. Applications are also evaluated on the expertise of the research team and institutional resources supporting the project. Key dates include the first submission opening on January 5, 2025, with NIH standard due dates. Interested applicants are encouraged to submit a Letter of Intent 30 days before the due date.