Discovery of in vivo Chemical Probes for the Nervous System (R01 Clinical Trial Not Allowed) | PAR 24 088

Opportunity Information: Apply for PAR 24 088

The NIH grant opportunity "Discovery of in vivo Chemical Probes for the Nervous System (R01 Clinical Trial Not Allowed)" (PAR-24-088) supports research teams working on the discovery and development of small-molecule chemical probes that can function in living systems, with a specific focus on the nervous system and brain-relevant targets. The central idea is to move beyond purely in vitro tool compounds and instead generate optimized, biologically useful molecules that can be used in vivo to interrogate how specific targets and pathways contribute to normal brain function and to disease-related processes. The program is positioned as a probe-discovery and target-validation effort rather than a clinical testing program, and it explicitly does not allow clinical trials under this announcement.

A key expectation is that applicants are not starting from scratch. Proposed projects should already have "starting compounds" in hand, meaning validated hits or early leads that show meaningful activity on the target of interest, along with established bioassays that can be used to test and compare newly synthesized analogs. In practical terms, NIH is looking for teams that can immediately begin medicinal chemistry optimization and iterative testing, rather than spending the early project period solely on primary screening or assay development. The intent is to accelerate progress toward robust, selective, and usable in vivo probes that can reliably modulate a target in the brain (or nervous system more broadly) and produce interpretable biological readouts.

The scientific goals of the NOFO fall into two closely linked areas. First, it aims to stimulate the discovery and development of novel small molecules that can serve as chemical probes to understand biological processes aligned with the missions of several NIH institutes: 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). Second, it supports discovery and/or validation of novel biological targets that can inform mechanistic studies of brain and nervous system disease. A strong application, in other words, is not only about making a better compound; it is also about using that compound to produce clearer causal evidence about how a specific molecular target influences disease-relevant biology, pathways, or phenotypes. NIH indicates that emphasis will be placed on projects that deliver new insight into important disease-related targets and processes, suggesting that applications should clearly connect probe development to a meaningful biological question with relevance to mental health, substance use, vision/eye-related neuroscience, aging, or neurodegeneration.

The mechanism is an NIH R01 research project grant, categorized under Education and Health funding activities, and associated with CFDA numbers 93.242, 93.279, 93.866, and 93.867. The opportunity is listed as discretionary and uses a grant funding instrument. While the provided source data does not specify an award ceiling or the expected number of awards, it does provide the application window context, with an original closing date of 2027-01-07, indicating that NIH intends this to be an ongoing opportunity over multiple receipt dates rather than a single one-time competition.

Eligibility is broad and includes a wide range of domestic and non-domestic organizations. Eligible applicants include state, county, city, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations (including those other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; and small businesses. The announcement also explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, tribal governments other than federally recognized entities, and foreign organizations (non-U.S. entities). This breadth signals an intent to attract multidisciplinary teams and to lower barriers for a wide range of institutions that can contribute strong chemistry, pharmacology, and neuroscience capabilities.

Overall, the program is best understood as support for translationally minded basic research: developing and refining small-molecule tools that work in vivo, using them to validate or illuminate novel nervous system targets, and generating mechanistic insights that can clarify brain disease biology. The strongest fits are projects that already have credible starting matter and assays, can demonstrate a realistic optimization and testing plan, and can explain how an in vivo-ready probe will unlock answers about a target or pathway that currently cannot be resolved with existing tools.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Discovery of in vivo Chemical Probes for the Nervous System (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.279, 93.866, 93.867.
• This funding opportunity was created on 2023-12-13.
• Applicants must submit their applications by 2027-01-07.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 24 088

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