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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.

NIMH Drug and Device Development Pipeline
NIMH-specific Resource    
Multiple NIH Institutes/Centers
Target ID

Target ID: Identification of molecules that play a role in a disease processes.

Assay Development

Assay Development: Development of an experimentally controlled biochemical or biological system used for the quantitative analysis of test samples.

HTS

HTS: High throughput screening - a method in which a large number of assays (1000-1M) are performed and assessed in a relatively short time period, using automated technologies.

Hit to Lead

Hit to Lead: Progression from discovery of a compound whose activity exceeds a predefined threshold, to the identification of a compound within a series with sufficient pharmacological and biological characteristics to progress to a full drug development program.

Lead Optimization

Lead Optimization: Process in which the drug-like properties of an initial lead or lead series are improved and compounds with favorable chemical, pharmacological, and toxicological profiles are identified for progression to the clinic.

Pre-Clinical

Pre-Clinical: Testing of compounds in experimental systems for their biological and toxic effects and potential clinical applications.

Phase I

Phase I: Assessment of drug safety and tolerability. Drugs are tested in a small group of healthy volunteers to determine the drug's activity. Related “first-in-human” studies may also assess target engagement and pharmacological effects.

Phase II

Phase II: Typically double-blinded, placebo-controlled studies designed to continue Phase I safety assessments, to determine how well the drug works in patients, and to identify the optimal dose to be used in Phase III clinical trials.

   

Provides screening of novel psychoactive compounds for pharmacological and functional activity at cloned human or rodent CNS receptors, channels, and transporters. Assays also available for bioavailability predictions and cardiovascular toxicity predictions.

Synthesizes and distributes novel research chemicals, psychoactive drugs, and compounds including support for radiochemistry, and limited medicinal chemistry and GMP synthesis.

 

Provides toxicology and safety assessment of promising, target-selective compounds for use as imaging ligands in human studies. The program also provides limited ADME toxicology, and PK support for early drug and ligand discovery.

 
     

Supports experimental medicine-based first-in-human and proof-of-concept studies of novel mechanism of action investigational drugs or devices to attract private funding for further clinical development as FDA-approved treatments. Also supports testing of novel drugs for use in pediatric populations with psychiatric disorders.

           

Supports experimental therapeutics-based pilot studies of novel pharmacologic interventions and devices as well as behavioral, biologics-based, cognitive, interpersonal, physiological, or combined approaches. Trials must be designed so that results, whether positive or negative, will provide information of high scientific utility and will support “go/no-go” decisions about further development or testing of the intervention.

Supports small businesses/biotechnology companies in the development of high throughput tools for compound screening, target identification, novel technologies for evaluating compounds in clinical trials, and drug discovery/development.

Accelerating basic and translational scientific discoveries with a plan to advance drug therapeutics for HIV-Associated Neurocognitive Disorders (HAND).

National Cooperative Drug Discovery and Development Groups (NCDDG) ( U19 , UM1 )

Advancing the discovery, preclinical development, and proof of concept testing of new candidate medications to treat mental disorders or drug or alcohol addiction, and to develop novel ligands as tools to further characterize existing or to validate new drug targets.

Supports development of novel, robust analytical platforms, using in vitro assays to measure neurobiological endpoints and build a pipeline to be used in the context of target identification and drug discovery.

   

Bridging Interventional Development Gaps: provides access to government-funded contract resources for generating data and clinical material that investigators need to file an IND application with the FDA.

   

Supports development of assays for specific biological targets and disease mechanisms with intent to screen for small molecule compounds that show potential as probes for use in advancing knowledge about the known targets, identifying new targets, or as pre-therapeutic leads.

     
 
Drug Discovery for Nervous System Disorders ( R01 , R21 )

Supports studies aimed at translating basic science findings into the conceptualization, discovery, and preclinical evaluation of innovative therapeutics for nervous system disorders, with the goal of accelerating the development of new treatments.

The NIH Clinical Collection is a plated array of approximately 450 small molecules that have a history of use in human clinical trials.

Provides rapid access via the Fast Track mechanism to HTS resources of the MLPCN for projects that meet the goals of the Assay Development for HTS Program.

         
 
HTS Assay
( R01 , R21  )

Supports high throughput screening assay implementation and hit validation through a joint effort between the investigator developing the assay and the screening facility responsible for HTS implementation of the assay.

Supports optimization of hits using integrated biological and chemical examination of structure activity relationships to develop novel in vivo chemical probes.

The Network bridges the gap in drug development between academic and industry research, offering researchers a “virtual pharma” to develop promising hit compounds from chemical optimization through Phase I clinical testing.

 
 

Offers access to the large-scale screening capacity, along with medicinal chemistry and informatics necessary to identify chemical probes to study the functions of genes, cells, and biochemical pathways.

The program creates a drug development pipeline within the NIH to stimulate research collaborations with academic scientists, non-profit organizations, and pharmaceutical and biotechnology companies working on rare and neglected illnesses.

 

PubChem is a component of the NIH Molecular Libraries Roadmap Initiative. It provides information on the biological activities of small molecules. PubChem is organized as three linked databases within the NCBI’s Entrez information retrieval system.

   

Strategic Plan

Reports

Extramural Divisions Supporting Therapeutics Research and Trials

Information Relevant to Therapeutics Discovery FOAs

Additional Funding Announcements and Notices Relevant to Therapeutics Discovery