PAR-25-063
Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders (R01 Clinical Trial Not Allowed)
Summary
PAR-25-063: Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders
Research Focus
NIMH seeks to support early-stage drug discovery research targeting mental illness through development and validation of screening assays that identify chemical hits—compounds with confirmed desired activity in orthogonal assays—suitable for future drug development. The program covers three integrated stages: assay development, primary screen implementation, and hit validation. Research should address psychiatric disorders including treatment-resistant depression, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), panic disorder, and autism spectrum disorders.
Assays may be target-based (measuring receptor-ligand binding, enzyme activity, ion channel function, protein-protein interactions), pathway-based, or phenotype-based, using diverse platforms from cell-free systems and cultured cells to induced pluripotent stem cells (iPSCs), organoids, brain slices, and model organisms (zebrafish, Caenorhabditis elegans, Drosophila melanogaster). Detection methods include fluorescence, luminescence, FRET, TR-FRET, flow cytometry, electrophysiology, and biophysical measures. Primary screening may employ high-throughput screening (HTS), moderate-throughput screening (MTS), or virtual screening using computational approaches (machine learning, QSAR, protein-ligand docking). Hit validation requires orthogonal assays and medicinal chemistry assessment to eliminate false positives and undesirable chemotypes (PAINS compounds).
At-a-Glance
- Who can apply: Not stated (see full FOA for institutional eligibility)
- Funding & project length: Not stated
- Award mechanism: R01 Research Project Grant (clinical trials not allowed)
- Key dates: Applications due February 5, 2025 (earliest); June 5, 2025; October 5, 2025; February 5, 2026 (rolling deadlines); expiration May 8, 2026
- Best fit for: Neuroscience, chemical biology, and drug discovery researchers developing screening assays for psychiatric disorder targets; requires preliminary assay characterization and pilot screen data
Key Facts
Deadline
Thu, May 7, 2026
Posted
Wed, November 6, 2024
Award / Year (direct costs)
$250,000
Max Total
$1,250,000
Max Duration
5 years
Keywords
Research Areas
Gotchas (5)
Primary screen implementation projects require preliminary data demonstrating that a primary screen has been developed, fully characterized, and tested in a pilot format
90%
Source Text
“Projects focusing on screen implementation are required to provide preliminary data demonstrating that a primary screen has been developed, fully characterized, and tested in a pilot format.”
Virtual screening projects have a mandatory collaboration requirement: applicants proposing virtual screening 'must collaborate with hit assay validation and medicinal chemistry experts for experiment
95%
Source Text
“Projects proposing the use of VS, either ligand-based screening or receptor-based screening, must collaborate with hit assay validation and medicinal chemistry experts for experimental testing of the proposed in silico hits.”
Phenotypic screening has a conditional requirement: it 'should only be proposed if a target deconvolution is included in the application or there is a strong association between the mechanisms that dr
90%
Source Text
“Phenotypic screening should only be proposed if a target deconvolution is included in the application or there is a strong association between the mechanisms that drive the phenotypic assay, the preclinical disease model and the human disease.”
Clinical trials are explicitly not allowed under this R01 mechanism
95%
Source Text
“Assay Development and Screening for Discovery of Validated Chemical Hits for Brain Disorders (R01 Clinical Trial Not Allowed)”
In vivo whole organism assays (zebrafish, C. elegans, Drosophila) are restricted to situations where they 'adequately recapitulate important aspects of neuronal or glial function and are needed to dem
85%
Source Text
“In vivo whole organism assays (e.g., zebrafish, Caenorhabditis elegans (C. elegans) and Drosophila melanogaster) should only be proposed if they adequately recapitulate important aspects of neuronal or glial function and are needed to demonstrate the biological or physiological effects of validated hit compound(s).”