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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.

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.

NoticesAssay DevelopmentHTS/MTS and Hit discoveryTool/Probe DevelopmentBiomarkers Development
Psychedelics and Related Compounds NOT-MH-23-125   
NIMH’s Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Preclinical Studies NOT-MH-19-053    
PreClinical Research on Gene Therapies for Rare Genetic Neurodevelopmental Disorders NOT-MH-23-235    
PreClinical Research on Gene Therapies for Rare Genetic Neurodevelopmental Disorders NOT-MH-23-236    
Program AnnouncementsAssay DevelopmentHTS/MTS and Hit discoveryTool/Probe DevelopmentBiomarkers Development
In vivo Preclinical Assays of Circuit Engagement PAR-23-091    
Assays to Address Gaps in Treatment Development PAR-23-087    
Engineering Human Nervous System Microphysiological Systems PAR-23-046    
Engineering Human Nervous System Microphysiological Systems PAR-23-047    
Discovery of Chemical Hits PAR-23-168   
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-164 
* See also Hit-to-Lead table
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-165 
* See also Hit-to-Lead table
National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental or Alcohol Use Disorders PAR-22-143 
* See also Hit-to-Lead table
National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental or Alcohol Use Disorders PAR-22-144 
* See also Hit-to-Lead table
Small Business Program SBIR & STTR
* See also Hit-to-Lead table
Illuminating the Druggable Genome  
Tasks Relevant to Anhedonia (PAR-20-235)    
Discovery of in vivo Chemical Probes for the Nervous System PAR-24-088    

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.

NoticesMed Chem/SAR to improve Target Activity and SelectivityIn vitro/in vivo DMPKIn vitro toxicity studiesNovel Delivery SystemsPharmacodynamic Measures
Psychedelics and Related Compounds NOT-MH-23-125   
Program AnnouncementsMed Chem/SAR to improve Target Activity and SelectivityIn vitro/in vivo DMPKIn vitro toxicity studiesNovel Delivery SystemsPharmacodynamic Measures
Psychoactive Drug Screening Program     
Chemical Synthesis Program     
Neuromodulation/ Neurostimulation Device Development for Mental Health Applications PAR-22-038 
Neuromodulation/ Neurostimulation Device Development for Mental Health Applications PAR-22-039 
Discovery and Development of Drug Leads PAR-22-032  
Discovery and Development of Drug Leads PAR-22-031  
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-164  * See also Biology to Therapeutics table
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-165 
* See also Biology to Therapeutics table
National Cooperative Drug/ Device Discovery/ Development Groups (NCDDG) for the Treatment of Mental or Alcohol Use Disorders PAR-22-143 
* See also Biology to Therapeutics table
National Cooperative Drug/ Device Discovery/ Development Groups (NCDDG) for the Treatment of Menta l or Alcohol Use Disorders PAR-22-144 
* See also Biology to Therapeutics table
Small Business Program SBIR & STTR
* See also Biology to Therapeutics table
Blueprint Neurotherapeutics Network for Small Molecules  
Blueprint Neurotherapeutics Network for Biologics  
HEAL Initiative: Planning Studies for Initial Analgesic Development Initial Translational Efforts R34  RFA-NS-21-016 
HEAL Initiative: Team Research for Initial Translational Efforts in Non-addictive Analgesic Therapeutics Development U19  RFA-NS-21-015 
In vivo Preclinical Assays of Circuit Engagement PAR-23-091     
Assays to Address Gaps in Treatment Development PAR-23-087     

Strategic Plan

Extramural Divisions Supporting Therapeutics Research and Trials

Information Relevant to Therapeutics Discovery FOAs