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.
|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: 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: 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.
|Phase III & IV |
Phase III & IV: Phase III studies definitively determine a drug's effectiveness and side-effect profiles. Phase IV involves post-marketing surveillance studies to detect any rare or long-term adverse effects in a larger population.
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 new mechanism of action, IND-ready candidate medications to treat mental disorders.
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).
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 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.
Solicits projects to directly access medicinal chemistry resources provided by the MLPCN via the Fast Track mechanism.
Supports evaluation of feasibility, tolerability, and safety of novel mechanism drug candidates, or novel psychosocial strategies for treating mental disorders and obtaining data for planning larger-scale intervention or services studies.
Promotes the development of automated screening projects that can be submitted to the MLPCN.
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.
- 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
Extramural Divisions Supporting Therapeutics Research and Trials
- Division of Neuroscience and Basic Behavioral Science (DNBBS)
- Division of Adult Translational Research and Treatment Development (DATR)
- Division of Developmental Translational Research (DDTR)
- Division of AIDS Research (DAR)
- Division of Services and Intervention Research (DSIR)
Information Relevant to Therapeutics Discovery FOAs
- PA-13-157, PA-13-158, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R21, R21/R33)
- CNS Radiotracer Table: A table of CNS radiotracers that have been advanced for use in human studies.
- PAR-13-086, PAR-13-087, National Cooperative Drug Discovery and Development Groups (NCDDG) (U19, UM1)
- PAR-13-048, PAR-13-049, Drug Discovery for Nervous System Disorders (R01, R21)
- Lead Compound Report Card (PDF file): 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 (PDF file): A graphical illustration of the comprehensive series of assays used for lead optimization and candidate selection.
- PAR-13-643, National Cooperative Reprogrammed Cell Research Groups (NCRCRG) to Study Mental Illness (U19)
Additional Funding Announcements and Notices Relevant to Therapeutics Discovery
- Translational Research for the Development of Novel Interventions for Mental Disorders (R21/R33)
- Research Domain Criteria (RDoC) Project — description of the project, workshop proceedings, current RFAs, and more information.
NIH and NIMH Resources for Therapeutics Development
ChemNavigator allows investigators to search a database of commercially available drug discovery screening compounds. It includes a new Semi-Custom Synthesis Online Request System (SCOSRS) option that links investigators with companies capable of synthesizing specific compounds at reasonable costs.
- Limited Access Datasets from NIMH Clinical Trials
- NIMH requires all investigators seeking access to data from NIMH-supported trials held by NIMH to execute and submit as their request the appropriate Data Use Certification pertaining to the trial. The datasets distributed by NIMH are referred to as “limited access datasets” because access is limited to qualified researchers who complete Data Use Certifications.
ClinicalTrials.gov is a registry of federally and privately supported clinical trials conducted in the United States and around the world. ClinicalTrials.gov provides information about a trial's purpose, who may participate, locations, and phone numbers for more details.
Lead Compound Report Card (PDF file): 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 (PDF file): A graphical illustration of the comprehensive series of assays used for lead optimization and candidate selection.
National Institute of Neurological Disorders and Stroke (NINDS) Grant Policy update: Improving the Quality of NINDS-Supported Preclinical and Clinical Research through Rigorous Study Design and Transparent Reporting (PDF file).