Molecular Pharmacology Research Program

This program supports research aimed at and the discovery, design, development, and testing of novel compounds for use as neuroimaging or pharmacological research tools or candidate therapeutics for mental illnesses. The program also supports the development and use of assays for interrogating novel biological targets.

Areas of interest include:

• Discovery and development of novel in vivo chemical probes to discover and/or validate novel biological targets that will inform studies of brain disease mechanisms.
• Design, synthesis, and characterization of candidate therapeutics for novel and emerging targets relevant to mental illnesses.
• Isolation, identification, and characterization of compounds derived from natural products.
• Molecular modeling and computational chemistry.
• Isolation and characterization of endogenous ligands.
• Development and evaluation of novel chemical delivery systems.
• Implementation of innovative biological, biophysical or cell-based assays for novel biological targets.
• Implementation of primary screens to identify initial screening hits (high throughput target-focused screens, or moderate throughput screens).
• Preliminary evaluation of candidate compounds using screening assays (e.g., biochemical and cellular assays, modified model organisms, and electrophysiological or behavioral systems).
• Development and testing of PET/SPECT imaging ligands for novel targets implicated in mental illnesses in proof of concept studies as potential biomarkers for drug discovery and for pathophysiological studies of mental illnesses.
• Implementation and application of gene editing technologies to target therapeutics for psychiatric disorders.

High-priority areas include the development of probes and/or early drug leads for novel molecular or circuit-based targets relevant to mental illnesses, including targets identified through human genetic studies. Studies incorporating the use of novel assays to assess activity of ligands in relevant circuits, systems, and/or domains of function are encouraged. Incorporation of concurrent biomarker development is encouraged, when feasible, for early-stage drug discovery efforts.

Studies aimed at the development of new ligands for targets where a high-quality probe or therapeutic already exists are generally of lower priority.

Research Resources:

This program also provides a range of research resources, including the screening of novel psychoactive compounds at CNS receptors, channels, and transporters; the synthesis and distribution of psychoactive compounds to support basic and clinical research; and the assessment of promising compounds for toxicity and safety for use in human studies.

Research resources supported by the program include:

• NIMH Psychoactive Drug Screening Program  – provides screening of novel psychoactive compounds for pharmacological and functional activity at cloned human or rodent CNS receptors, channels, and transporters. Assays are also available for bioavailability predictions (CaCo2, MDR-1) and cardiovascular toxicity predictions (HERG, 5-HT2B). The program also supports a database of affinity constants for ligand binding.
• NIMH Chemical Synthesis and Drug Supply Program  – synthesizes and distributes novel research chemicals, psychoactive drugs, and compounds that unavailable or difficult to obtain from commercial sources.

The program also supports drug discovery and optimization projects through the NIH Blueprint Neurotherapeutics Program , which provides projects with a coordinated set of grant, contract, and consultant resources to move new therapeutics toward clinical development.

It is recommended that applicants review the NIH/NIMH Therapeutics Discovery Research webpage for relevant announcements and guidance.

Applications should adhere to recently published recommendations detailed in a notice in the NIH Guide (NOT-MH-14-004  ) and summarized in Enhancing the Reliability of NIMH-Supported Research through Rigorous Study Design and Reporting on the NIMH website as well as NIMH guidance on the use of model organisms for mental health-relevant research (NOT-MH-19-053 ).

Applicants are strongly encouraged to discuss their proposals with the Institute contact listed below prior to the submission of their application to ascertain that their proposed work is aligned with NIMH funding priorities.

Molecular Pharmacology Program Contact

Enrique Michelotti, Ph.D.
Program Chief
6001 Executive Boulevard
301-443-5415 michelottiel@mail.nih.gov

Research Resources Contact

Jamie Driscoll, B.A.
6001 Executive Boulevard
301-443-5288, jdrisco1@mail.nih.gov