Preclinical Screening for Natural Product Drug Interactions (Clinical Trial Not Allowed, R21) | RFA AT 20 001

Opportunity Information: Apply for RFA AT 20 001

The NIH opportunity titled "Preclinical Screening for Natural Product Drug Interactions (Clinical Trial Not Allowed, R21)" (Funding Opportunity Number RFA-AT-20-001) supports early-stage, exploratory research aimed at spotting natural products that could cause drug interactions by changing how the body metabolizes or transports conventional medications. The core scientific goal is to identify natural products that inhibit or induce key Phase I and Phase II drug-metabolizing enzymes, as well as drug transporters, since those mechanisms are a common pathway for pharmacokinetic interactions that can raise drug levels to unsafe ranges or reduce them below effective levels. The work is explicitly preclinical and in vitro, with no clinical trials allowed, and is designed to generate actionable screening data that can help prioritize which natural products need deeper investigation.

Projects are expected to focus on laboratory screening approaches, including medium- to high-throughput assays, to evaluate libraries of complex botanical or natural product extracts and/or purified constituents. A major emphasis is on practical, scalable methods that can flag interaction potential across many samples rather than only studying a single product in depth. The FOA also allows work that goes beyond screening to isolate and chemically identify the specific active constituents responsible for the interaction signal, particularly when the active compounds are novel, not well characterized, or not commercially available. In other words, applicants can propose workflows that start with complex mixtures, detect enzyme or transporter effects, and then perform bioactivity-guided fractionation and identification to pinpoint the interacting molecules.

This announcement is part of a larger NCCIH investment that includes a U54 Center of Excellence for Natural Product Drug Interaction Research. A key expectation is that data generated under these R21 projects will be uploaded to, and shared through, the public data repository maintained by the U54 Center. That requirement signals that the program is building a community resource, not just funding isolated projects, and that applicants should plan for standardized data capture, quality control, and timely data deposition so results can be compared and reused by other researchers and stakeholders.

The award mechanism is the NIH R21 exploratory/developmental grant, and the listed award ceiling is $200,000. The opportunity falls under the Health funding activity category (CFDA 93.213) and is offered by the National Institutes of Health. The original closing date shown for the competition was 2019-11-01, and the FOA creation date is 2019-07-23, which helps situate it historically if someone is using it as a model for similar current opportunities or looking for related reissued announcements.

Eligibility is broad and includes many types of U.S.-based organizations and government entities, such as state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofit organizations (with or without 501(c)(3) status); for-profit organizations (other than small businesses); small businesses; and Native American tribal governments (federally recognized) and tribal organizations (other than federally recognized tribal governments). The FOA also highlights additional eligible applicant categories often emphasized in NIH programs, including Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, HBCUs, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions.

Foreign eligibility is restricted in a specific way. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply as the applicant organization. However, foreign components, as defined in the NIH Grants Policy Statement, are allowed, meaning a U.S. applicant may include certain foreign collaborations or activities if they meet NIH definitions and requirements. This structure supports international scientific expertise when justified, while keeping the primary awardee organization domestic.

Overall, the program is designed to improve understanding of which commonly used or emerging natural products might alter drug exposure through enzyme and transporter pathways, using robust in vitro screening and, when needed, compound isolation and identification. The practical deliverable is a set of publicly shared screening and characterization data that can inform subsequent mechanistic studies, risk assessment, and eventually better guidance for clinicians, patients, and researchers about potential natural product-drug interaction risks.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Preclinical Screening for Natural Product Drug Interactions (Clinical Trial Not Allowed, R21)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213.
• This funding opportunity was created on 2019-07-23.
• Applicants must submit their applications by 2019-11-01. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $200,000.00 in funding.
• 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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