Opportunity Information: Apply for PAR 27 081
The NIH funding opportunity PAR-27-081, titled "Discovery of in vivo Chemical Probes for the Nervous System (R01 Clinical Trial Not Allowed)," supports research teams working to create and refine small-molecule chemical probes that can be used in living systems to study the nervous system and brain disease biology. The core idea is to accelerate the discovery of tools that help researchers understand how specific brain targets work in vivo, especially targets that are novel, poorly characterized, or strongly connected to disease-relevant mechanisms. Rather than funding very early exploratory chemistry, this program is geared toward projects that are already past the earliest stage of discovery and are ready for focused optimization and rigorous biological testing.
A key expectation is that applicants already have starting compounds in hand, described as validated hits, along with bioassays that can be used to evaluate newly synthesized analogs. In practical terms, NIH is looking for proposals where there is credible preliminary evidence that the starting molecule engages the intended target or produces a relevant biological effect, and where the team can move quickly into medicinal chemistry optimization paired with iterative testing. This includes improving properties needed for in vivo use, such as potency, selectivity, exposure, stability, and brain penetration, while using fit-for-purpose assays to confirm target engagement and biological relevance.
The scientific scope emphasizes two related outcomes. First, the discovery and development of novel small molecules as chemical probes to illuminate biological processes aligned with the missions of 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, the discovery and/or validation of new biological targets that can clarify mechanisms underlying brain disorders. The program places particular weight on projects likely to generate fresh insight into disease-related targets and processes, meaning the strongest applications will connect the probe-development plan to a clear biological question and show how the resulting probe will enable mechanistic studies that would otherwise be difficult or impossible.
This is an R01 grant mechanism and explicitly does not allow clinical trials, so the supported work is intended to remain in the preclinical or translational tool-building space rather than testing interventions in humans. The opportunity is listed as discretionary funding and falls under NIH health research activity areas, with CFDA numbers 93.242, 93.279, 93.866, and 93.867, reflecting participation across multiple NIH institutes.
Eligibility is broad and includes many U.S. organization types, such as state, county, and local governments; public and private institutions of higher education; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (including those other than small businesses); small businesses; tribal governments and tribal organizations; independent school districts; and public housing authorities/Indian housing authorities. International participation is also permitted: non-U.S. (foreign) organizations may apply, non-U.S. components of U.S. organizations are eligible, and foreign components are allowed as defined in the NIH Grants Policy Statement. The opportunity lists an original closing date of 2027-03-05, and it was created on 2026-05-04. No award ceiling or expected number of awards is specified in the provided source data.Apply for PAR 27 081
- The National Institutes of Health in the 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 2026-05-04.
- Applicants must submit their applications by 2027-03-05.
- 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.
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FAQs: NIH PAR-27-081 - Discovery of in vivo Chemical Probes for the Nervous System (R01 Clinical Trial Not Allowed)
What is PAR-27-081?
PAR-27-081 is an NIH funding opportunity titled "Discovery of in vivo Chemical Probes for the Nervous System (R01 Clinical Trial Not Allowed)." It supports research teams developing and refining small-molecule chemical probes that can be used in living systems (in vivo) to study the nervous system and brain disease biology.
What is the main goal of this funding opportunity?
The goal is to accelerate the discovery of practical in vivo research tools (small-molecule probes) that help scientists understand how specific brain targets work in living systems. The program prioritizes targets that are novel, poorly characterized, or strongly tied to disease-relevant mechanisms.
What type of grant mechanism is used?
This opportunity uses the NIH R01 research project grant mechanism.
Are clinical trials allowed under this R01?
No. The funding opportunity explicitly states "Clinical Trial Not Allowed." Supported work is intended to stay in the preclinical or translational tool-building space rather than testing interventions in humans.
What kinds of projects are a good fit for PAR-27-081?
Projects are a strong fit when they already have credible starting chemistry and are ready for focused optimization and rigorous biological testing. NIH is looking for teams that can move quickly into medicinal chemistry optimization paired with iterative testing to improve in vivo performance and demonstrate biological relevance.
Is this opportunity meant for very early exploratory chemistry?
No. The program is not geared toward very early exploratory chemistry. It is aimed at projects that are already past the earliest stage of discovery and are ready for structured optimization and validation work.
What does NIH expect applicants to already have before applying?
A key expectation is that applicants already have starting compounds in hand, described as validated hits, along with bioassays that can evaluate newly synthesized analogs. In practice, NIH expects preliminary evidence that the starting molecule engages the intended target or produces a relevant biological effect.
What is meant by "validated hits" in this context?
Based on the description provided, "validated hits" refers to starting compounds with credible preliminary evidence of target engagement or a relevant biological effect, supported by assays that can be used to guide further medicinal chemistry and iterative biological testing.
What kinds of improvements are expected during probe optimization?
The opportunity highlights improving properties needed for in vivo use, including potency, selectivity, exposure, stability, and brain penetration, while confirming target engagement and biological relevance using fit-for-purpose assays.
Why is in vivo use emphasized?
The program is focused on creating probes that work in living systems so researchers can study nervous system targets and disease biology under biologically relevant conditions, rather than only in vitro.
What are the two main scientific outcomes emphasized by the program?
The scientific scope emphasizes: (1) discovery and development of novel small molecules as chemical probes aligned with the missions of participating NIH institutes, and (2) discovery and/or validation of new biological targets that clarify mechanisms underlying brain disorders.
Which NIH institutes are specifically referenced in the scientific scope?
The opportunity aligns with missions of 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).
Does the program support work on new or poorly characterized targets?
Yes. The description places special emphasis on targets that are novel, poorly characterized, or strongly connected to disease-relevant mechanisms, particularly where an in vivo probe could unlock mechanistic understanding.
How important is the biological question behind the probe?
Very important. The program places particular weight on projects likely to generate fresh insight into disease-related targets and processes. Strong applications are expected to connect the probe-development plan to a clear biological question and show how the resulting probe will enable mechanistic studies that would otherwise be difficult or impossible.
What kind of testing approach does NIH expect during the project?
NIH expects medicinal chemistry optimization paired with iterative testing using fit-for-purpose assays. The assays should be able to evaluate newly synthesized analogs and help confirm target engagement and biological relevance as the probe is optimized for in vivo performance.
What does "fit-for-purpose assays" mean here?
In the context provided, it means assays that are appropriate and practical for guiding medicinal chemistry optimization and for confirming that new analogs engage the intended target and produce biologically relevant effects, especially in support of in vivo use.
What activity area does this opportunity fall under?
It is listed under NIH health research activity areas and is described as discretionary funding.
What CFDA numbers are associated with this opportunity?
The opportunity lists CFDA numbers 93.242, 93.279, 93.866, and 93.867, reflecting participation across multiple NIH institutes.
Who is eligible to apply?
Eligibility is broad and includes many U.S. organization types, including state, county, and local governments; public and private institutions of higher education; nonprofit organizations (with or without 501(c)(3) status); for-profit organizations (including those other than small businesses); small businesses; tribal governments and tribal organizations; independent school districts; and public housing authorities/Indian housing authorities.
Can international (non-U.S.) organizations apply?
Yes. Non-U.S. (foreign) organizations may apply. Non-U.S. components of U.S. organizations are eligible, and foreign components are allowed as defined in the NIH Grants Policy Statement.
Are foreign components allowed on an otherwise U.S.-based application?
Yes. The opportunity states that foreign components are allowed as defined in the NIH Grants Policy Statement.
What is the original closing date listed for this opportunity?
The original closing date provided is 2027-03-05.
When was this funding opportunity created?
The opportunity was created on 2026-05-04.
Is there an award ceiling listed?
No award ceiling is specified in the provided source data.
Is the expected number of awards listed?
No. The provided source data does not specify an expected number of awards.
What stage of research does NIH appear to be prioritizing?
The description prioritizes projects beyond the earliest discovery stage, where teams already have starting compounds and assays and can focus on optimization and rigorous biological testing aimed at generating an in vivo-ready chemical probe.
What is the intended value of the resulting chemical probe?
The intended value is to provide a small-molecule tool that enables in vivo mechanistic studies of nervous system targets and brain disease biology, helping researchers learn how specific targets work and how they connect to disease-relevant processes.
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