Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders (R01 Clinical Trial Not Allowed)

The NIH's National Institute of Mental Health (NIMH) has issued a Notice of Funding Opportunity (NOFO) titled "Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders." This NOFO seeks to fund projects focused on developing and validating high-throughput screening assays for discovering “hits”—chemical compounds with desired activity confirmed through orthogonal assays—that may serve as a foundation for future drug development targeting mental health disorders. Specifically, the NOFO covers the stages of assay development, primary screen implementation, and hit validation to support the discovery of novel compounds aimed at conditions like treatment-resistant depression, bipolar disorder, schizophrenia, PTSD, autism spectrum disorders, and other psychiatric disorders. The research objectives include developing innovative assays relevant to mental health drug discovery, implementing primary screens to identify initial hits, and validating these hits with additional assays and preliminary medicinal chemistry analysis. Eligible projects can utilize diverse assay types, including biochemical, cellular, or organismal screens, to examine compounds’ effects on various neuronal and glial functions. Virtual screening (VS) approaches that leverage computational methods and publicly available protein and small molecule data are also encouraged. Assay detection methods supported under this NOFO include fluorescence, luminescence, and flow cytometry, among others. The aim is for assays to accurately detect target-relevant activity with low rates of false positives and negatives, ultimately aiding the identification of promising lead compounds. Key dates include the earliest submission date of January 5, 2025, and the first application due date on February 5, 2025, with additional due dates throughout the year. Applications are reviewed in a multi-step process, including initial scientific merit review and final advisory council review. Award notices are anticipated as early as December 2025. This NOFO does not support clinical trials, and the project period can extend up to five years based on the scope of work. Eligible applicants include higher education institutions, nonprofits, small businesses, for-profit organizations, government entities, and foreign organizations. Applications from institutions such as HBCUs, Hispanic-serving institutions, and other minority-serving institutions are strongly encouraged. Foreign entities and foreign components within U.S.-based projects are also eligible. To apply, organizations must be registered with the System for Award Management (SAM), Grants.gov, and the NIH’s eRA Commons. Applications should address each stage of the discovery process, providing details on the assay’s design, scalability, and reproducibility, and a timeline for validation and hit progression. Proposals should also include a strategy for data management and sharing with the National Institute of Mental Health Data Archive (NDA) and are expected to adopt common data elements to facilitate broader data integration. Projects that focus on well-established targets, lack hit validation plans, or fail to verify chemical structures are considered nonresponsive. The review process will evaluate applications on significance, innovation, rigor, and feasibility, focusing on the scientific merit of the assay and screening approaches and the expertise of the research team. A robust rationale for the proposed targets and a clear path from discovery to validation are crucial, as is a comprehensive plan for validating hit compounds with cheminformatics and medicinal chemistry. Key review criteria include innovation in assay design, rigor in approach, and feasibility of execution. Applicants must submit complete and compliant proposals, following all instructions detailed in the How to Apply guide. Projects with direct costs exceeding $500,000 per year require prior approval from NIH. NIH policies on data sharing and human subject protections apply, and all recipients are responsible for adherence to federal requirements for non-discrimination and scientific integrity. This funding opportunity is administered under the Public Health Service Act and other relevant regulations, with awards contingent on NIH appropriations and programmatic priorities.