The National Institutes of Health (NIH) has reissued the funding opportunity for the Discovery of In Vivo Chemical Probes for the Nervous System (R01, Clinical Trial Not Allowed), aiming to support research in the discovery and development of small molecule chemical probes to better understand biological processes relevant to mental health, aging, drug addiction, and eye-related diseases. The NIH components participating in this initiative include the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), the National Eye Institute (NEI), and the National Institute on Aging (NIA). The primary focus is on chemical probes that can modulate novel biological targets to explore their roles in brain disease mechanisms. This funding opportunity is not for drug or therapeutic discovery but rather for developing chemical probes to gain insight into disease-related biological processes.

Applicants are required to have validated hit compounds in hand for chemical optimization and must have bioassays ready to test new analog compounds. The chemical optimization process will involve iterations of bioassay testing to refine the activity, specificity, and physicochemical properties of the compounds. The use of chemical probes for discovering and validating biological targets is encouraged, particularly for projects that provide new understanding of brain disease mechanisms. NIH emphasizes that this opportunity is intended for early-stage research in chemical probe development and is not suited for projects focused on later-stage drug development or extensive preclinical studies.

Each participating NIH institute has outlined its specific areas of interest. NIMH is focused on probes that target molecular or circuit-based pathways relevant to mental disorders like schizophrenia, bipolar disorder, autism, and PTSD, with a priority on targets for which there are no high-quality probes or therapeutics available. NIDA is interested in chemical probes for substance use disorders, seeking projects that target the discovery of novel biological mechanisms or potential pharmacotherapeutic leads for treating addiction. NIA focuses on probes related to age-related diseases, such as Alzheimer's disease, and is particularly interested in molecules that may help identify therapeutic targets for cognitive decline and other aging-associated conditions. NEI seeks probes to explore mechanisms underlying visual disorders, including diabetic retinopathy, glaucoma, and macular degeneration.

Eligible organizations include higher education institutions, non-profit entities, for-profit organizations, and government bodies. International organizations and non-domestic components of U.S.-based organizations are also eligible to apply. Applicants must submit their proposals through NIH's ASSIST system or via Grants.gov, adhering to NIH's application guidelines.

The funding mechanism is an R01 research project grant, with budgets not being limited but expected to reflect the actual needs of the proposed research. The maximum project period is five years, and the number of awards depends on NIH appropriations and the number of meritorious applications received. Applicants must follow NIH’s guidance on scientific rigor, reproducibility, and data sharing, with plans to submit all assay and probe data to public repositories such as PubChem.

Proposals will be reviewed based on scientific merit, innovation, the appropriateness of the proposed approaches, and the expertise of the research team. Key review criteria include the novelty and significance of the biological targets, the quality of the assays in place, the strength of the chemical optimization strategy, and the relevance of the proposed research to NIH priorities.