Assay development and screening for discovery of chemical probes, drugs or immunomodulators (R01 Clinical Trial Not Allowed) | PAR 20 271

Opportunity Information: Apply for PAR 20 271

This NIH funding opportunity (PAR-20-271) is an R01 grant aimed at early-stage small-molecule discovery work, specifically to find and validate compounds that either serve as chemical probes to help explain disease biology or act as agonists/antagonists of disease-relevant targets as potential starting points for therapy or immunotherapy. The central idea is to support discovery research that moves a project from a good biological hypothesis and an actionable assay all the way through screening and validation to a refined set of optimized "hit" compounds (and, where justified, early leads) that are credible and useful for health-related outcomes aligned with the missions of participating NIH Institutes. Clinical trials are not allowed under this FOA, so the work is expected to stay in the preclinical discovery and early translational space rather than testing interventions in human subjects.

The scope is broad but clearly organized around four main stages of the discovery pipeline. First is assay development, where applicants build, adapt, or optimize assays tied to specific biological targets or disease mechanisms. These assays are meant to be robust enough to support compound screening and should be designed with the intention of identifying small molecules that can function as research tools (chemical probes), help confirm or reveal targets, or serve as pre-therapeutic starting points. Second is screen implementation, which can include high-throughput, target-focused screening (typical of large library screening against a defined molecular target) as well as moderate-throughput approaches such as phenotypic screening (where the readout is a cellular or organismal phenotype rather than a single target) and fragment-based screening (starting with smaller chemical fragments that can later be elaborated). Third is hit validation, emphasizing the need to confirm initial screening "hits" through follow-up work: secondary assays that are orthogonal to the primary assay (to reduce false positives and assay-specific artifacts), deeper cheminformatics to analyze structures and relationships in the hit set, initial medicinal chemistry review to prioritize which compounds are worth pursuing, and additional experiments to clarify mode and mechanism of action. Fourth is hit-to-lead optimization, where structure-activity relationship (SAR) studies are used to improve potency, target engagement, and selectivity while reducing chemical liabilities. This stage can also include standard preclinical developability studies such as ADME (absorption, distribution, metabolism, excretion), PK (pharmacokinetics), and PD (pharmacodynamics), and when appropriate, in vivo models to test biological effects or early efficacy.

In practical terms, NIH is looking for projects that can produce a well-supported, reproducible set of validated small-molecule tools or candidate starting points rather than just a list of preliminary screening signals. Competitive applications typically align assay choice with a clear disease rationale, incorporate counter-screens and orthogonal confirmation early enough to avoid chasing artifacts, and include an explicit plan for how screening results will be triaged and advanced. The emphasis on cheminformatics and medicinal chemistry inspection signals that applicants should think beyond raw activity values and address issues like chemical tractability, structural alerts, selectivity risks, and whether a hit series is realistically optimizable.

Eligibility is expansive and includes many types of domestic U.S. organizations such as state, county, and local governments; public and private higher education institutions; independent school districts; special district governments; federally recognized tribal governments and other eligible tribal organizations; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The FOA also highlights additional eligible applicant groups, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, certain tribal governments that are not federally recognized, eligible federal agencies, and even non-U.S. entities (foreign organizations), indicating NIH is open to a wide range of institutional settings where strong discovery capabilities exist.

Administrative details from the source include: the sponsoring agency is the National Institutes of Health; the funding instrument is a grant under the discretionary category; the activity categories are listed as education and health; and the CFDA numbers associated with the opportunity include 93.173, 93.242, 93.279, 93.395, and 93.855. The opportunity was created on 2020-07-20, and the original closing date shown is 2023-01-07. The award ceiling and expected number of awards are not specified in the provided listing, which often means applicants should rely on the full FOA and NIH Institute/Center participation details for budget expectations and likely award volume.

Overall, this FOA supports the core work needed to go from a disease-relevant assay to credible, validated chemical matter, including the critical middle steps that often determine whether a project produces a true probe/lead series or stalls at unconfirmed hits. It is designed for teams that can integrate biology, screening operations, data science/cheminformatics, and medicinal chemistry to deliver compounds that are both scientifically informative and positioned for future preclinical advancement, without crossing into human clinical testing.

• 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): 93.173, 93.242, 93.279, 93.395, 93.855.
• This funding opportunity was created on 2020-07-20.
• Applicants must submit their applications by 2023-01-07. (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 20 271

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