Assay development and screening for discovery of chemical probes, drugs or immunomodulators (R01 Clinical Trial Not Allowed) | PAR 25 153

Opportunity Information: Apply for PAR 25 153

The NIH National Cancer Institute (NCI) is offering this R01 funding opportunity (PAR-25-153) to support early-stage drug discovery efforts focused on finding small molecules that can either serve as chemical probes to better understand disease biology or act as therapeutic or immunotherapy starting points by functioning as agonists or antagonists of a disease-relevant target. The overall aim is to move projects from a well-justified biological idea to a set of credible, validated small-molecule "hits" (and, where appropriate, more optimized lead-like compounds) that are relevant to health outcomes aligned with the missions of the participating NIH Institutes. This announcement explicitly does not allow clinical trials, so the work is expected to remain in the discovery and preclinical research space rather than testing interventions in human participants.

The NOFO is built around a fairly complete discovery pipeline and is meant to fund projects that can execute one or more stages of that pipeline with strong scientific rigor. A major entry point is assay development, where applicants design and validate assays tied to specific biological targets, pathways, or disease mechanisms. The expectation is that the assay is not just technically functional, but fit for screening and capable of identifying compounds that will be useful either as research tools (chemical probes) or as pre-therapeutic leads. From there, the NOFO supports implementation of screening, including high-throughput, target-focused screens as well as moderate-throughput approaches such as phenotypic screening and fragment-based strategies. In practice, this means applicants can propose different screening formats as long as the approach is justified for the biology and is likely to produce interpretable, actionable hits.

A key emphasis is hit validation and the steps needed to separate real biology from artifacts. Supported activities include running secondary assays that are orthogonal to the primary screening assay (for example, using a different readout or assay format to confirm the same biology), applying advanced cheminformatics to analyze and prioritize the hit set, and conducting an initial medicinal chemistry review to flag liabilities and focus resources on the most promising chemical matter. The NOFO also anticipates follow-up experiments to clarify how compounds work, including mode and mechanism of action studies, which can be especially important when hits come from phenotypic screens or when targets are uncertain.

Beyond initial validation, the opportunity also covers hit-to-lead optimization for projects that are ready to progress further. This includes structure-activity relationship (SAR) studies to improve potency and target engagement, improve selectivity, and reduce chemical liabilities. It also includes drug-discovery-enabling studies such as ADME (absorption, distribution, metabolism, and excretion), PK (pharmacokinetics), and PD (pharmacodynamics), and when scientifically appropriate, in vivo models to test biological effects or efficacy. The overall logic is to help teams move from a list of screening hits to more refined, better-characterized compounds that are credible tools for biology or realistic starting points for therapeutic development, without crossing into human clinical testing.

Eligibility is broad and includes many kinds of U.S. and non-U.S. organizations. Eligible applicants include federal, state, county, and local government entities; public and private institutions of higher education; independent school districts; special district governments; tribal governments (federally recognized) and tribal organizations (including some non-federally recognized categories); public housing authorities/Indian housing authorities; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses) as well as small businesses; and other organizational types. The NOFO also highlights additional eligible groups such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, U.S. territories or possessions, regional organizations, and foreign (non-U.S.) entities.

Administratively, this is an NIH discretionary grant using the R01 mechanism, listed under CFDA 93.395, and managed by NIH (with NCI as the soliciting institute). The original closing date provided is 2026-09-07. The public summary does not specify an award ceiling or the expected number of awards, so applicants would typically look to the full NIH posting for budget guidance, institute-specific expectations, and any additional review criteria or programmatic priorities that could shape competitiveness.

In plain terms, this opportunity is aimed at teams that can convincingly connect a cancer- or health-relevant biological question to a practical assay and screening strategy, then demonstrate a credible plan for confirming, characterizing, and improving the chemical matter that emerges. The deliverables are not simply "screening data," but a set of validated, well-understood hits (and potentially optimized leads) that can reliably advance biological understanding or serve as a foundation for future therapeutic development.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Assay development and screening for discovery of chemical probes, drugs or immunomodulators (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): 93.395.
• This funding opportunity was created on 2024-11-06.
• Applicants must submit their applications by 2026-09-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 25 153

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: