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) invites applications for the “Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders” under NOFO PAR-23-168. This opportunity focuses on developing and validating assays to identify chemical compounds, or “hits,” with potential to lead to new treatments for mental illnesses. These hits are compounds showing specific activity in an assay, which is confirmed by re-testing through orthogonal assays. The initiative includes three stages: (1) assay development, (2) primary screen implementation for initial hit identification, and (3) hit validation to establish compound activity. Importantly, no clinical trials are allowed under this NOFO. The goal of this NOFO is to encourage research focused on new drug discovery by supporting the creation of robust and reproducible assays for novel biological targets relevant to psychiatric disorders. Assay development may include target-based biochemical or cellular assays and cell- or organism-based assays designed to model the mechanisms of disorders like depression, schizophrenia, PTSD, bipolar disorder, and autism spectrum disorder. Assays can use a variety of technologies, including high-throughput screening (HTS) or moderate throughput screening (MTS), which may employ fluorescence, electrophysiology, or imaging techniques. Virtual screening approaches are also supported, encouraging computational methods, including machine learning, for initial hit identification. Eligible applicants include U.S.-based and foreign institutions, nonprofits, for-profit organizations, and higher education institutions. Researchers are encouraged to work with screening facilities for assay support and with experts in medicinal chemistry for hit assessment. Applicants should demonstrate preliminary data for assays, including pilot screening results and specific methodologies for testing compound interactions with disease targets. Assays that lack relevance to mental health targets or fail to verify compound structures are non-responsive to this NOFO and will not be reviewed. Applications are evaluated based on significance, innovation, and approach. Reviewers will assess whether the proposed targets are novel and significant for mental health research, the applicant’s expertise in relevant biological and chemical fields, and the technical soundness of the proposed assay and screening methodologies. Primary screen implementation should provide robust preliminary data, a clear hit validation path, and evidence that the selected library size and concentration cutoffs are justified. Hit validation should include verification of chemical structure, secondary assays, cheminformatics analysis, and medicinal chemistry input. Funding amounts are based on project needs, and there is no specified maximum budget limit; however, projects should propose timelines and budgets appropriate for the scope, with a maximum project period of five years. Applications requesting $500,000 or more in direct costs per year must notify NIH staff at least six weeks before submission. This NOFO requires that applicants comply with NIH data-sharing policies, including submission to the NIMH Data Archive (NDA), and include a Data Management and Sharing Plan. Submission deadlines align with NIH standard dates, and applicants are encouraged to submit early to allow time for error correction. For further information, applicants can contact designated scientific and grants management contacts at the NIMH.