NIH/NIMH Therapeutics Discovery Research
NIMH supports early-stage therapeutic discovery and development, through first-in-human and early efficacy trials for mental disorders. This web page details the range of NIMH programs and resources related to therapeutic discovery and development, as well as complementary programs available through broader NIH efforts.
Genes to biology
Target identification
Identification of a possible biological target and elucidating its role in disease. A target is a biochemical entity (a protein, RNA, or gene) to which a drug can bind and elicit a physiological change.
| Notices | Cellular Phenotypic | Circuit Pathology |
|---|---|---|
| Neuro-Glia Mechanisms Governing Complex Behaviors NOT-MH-22-090 | Checked | |
| AI for Decoding/ Modulating Neural Circuits NOT-MH-23-110 | Checked |
| Program Announcements | GWAS and Gene Variant Identification | Genomic Functional Annotation | Cellular Phenotypic | Circuit Pathology |
|---|---|---|---|---|
| Clinical Studies of Mental Illness PGC PAR-23-050 | Checked | |||
| PsychEncode Consortium | Checked | |||
| Cellular and Molecular Biology of Complex Brain Disorders PAR-24-024 Checked | Checked | Checked | Checked | |
| Cellular and Molecular Biology of Complex Brain Disorders PAR-24-025 | Checked | Checked | Checked | |
| SSPsyGene Consortium | Checked | Checked | Checked | |
| Temporal Dynamics of Coordinated Neural Activity PAR-21-175 | Checked | |||
| Temporal Dynamics of Coordinated Neural Activity PAR-21-176 | Checked |
Biology to Therapeutics
Lead Identification/ Target validation
Confirms that a molecular target is directly involved in a disease mechanism and that modulation of the target has a therapeutic effect.
| Notices | Assay Development | HTS/MTS and Hit discovery | Tool/Probe Development | Biomarkers Development |
|---|---|---|---|---|
| Psychedelics and Related Compounds NOT-MH-23-125 | Checked | Checked | ||
| NIMH’s Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Preclinical Studies NOT-MH-19-053 | Checked | |||
| PreClinical Research on Gene Therapies for Rare Genetic Neurodevelopmental Disorders NOT-MH-23-235 | Checked | |||
| PreClinical Research on Gene Therapies for Rare Genetic Neurodevelopmental Disorders NOT-MH-23-236 | Checked |
Biology to Therapeutics
Hit-to-Lead
Confirming structure-activity relationship (SAR) exists within several hit series for the biological target. In addition, an early assessment of in-vitro ADMET properties to help select the most promising leads for optimization.
Lead Optimization/Preclinical Development
The process of discovering a lead compound and progressing it towards a safe and efficacious drug therapy and successful commercialization into the market.
| Notices | Med Chem/SAR to improve Target Activity and Selectivity | In vitro/in vivo DMPK | In vitro toxicity studies | Novel Delivery Systems | Pharmacodynamic Measures |
|---|---|---|---|---|---|
| Psychedelics and Related Compounds NOT-MH-23-125 | Checked | Checked | Checked |
Small (Pilot) Clinical Trial
Preclinical Development
Process that links drug discovery in the lab to initiation of human clinical trials. Preclinical studies include, Process Development (select best synthetic route), new drug scale-up; select the best formulation, frequency, and duration of exposure; and support the intended clinical trial design.
Strategic Plan
- NIMH 2020 Strategic Plan for Research: Outlines the Institute’s research goals and priorities over the next five years.
Extramural Divisions Supporting Therapeutics Research and Trials
- Division of Neuroscience and Basic Behavioral Science (DNBBS)
- Division of Translational Research (DTR)
- Division of AIDS Research (DAR)
- Division of Services and Intervention Research (DSIR)
Information Relevant to Therapeutics Discovery FOAs
- From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses: Report of the National Advisory Mental Health Council's Workgroup on the next generation of interventions for mental disorders.
- Report of the National Advisory Mental Health Council Workgroup on Genomics: Guidance for applicants following the Report of the National Advisory Mental Health Council Workgroup on Genomics.
- Rigor and Reproducibility : Information to assist the extramural community in addressing rigor and transparency in NIH grant applications and progress reports.
- Research Domain Criteria (RDoC) Project: A description of the RDoC project, workshop proceedings, current Requests for Applications (RFAs), and additional information.
- NIMH NOT-MH-19-053 : Notice of NIMH’s Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Pre-clinical Studies.
- Central Nervous System (CNS) Radiotracer Table: A table of CNS radiotracers that have been advanced for use in human studies.
- Lead Compound Report Card: Use this form to summarize the characteristics of a lead compound you are studying and the desired characteristics of a therapeutic candidate, to track progress through the lead optimization process.
- Sample Drug Development Testing Funnel: A graphical illustration of the comprehensive series of assays used for lead optimization and candidate selection.