# Drug Transporters in Farm Animals

> **NIH FDA R43** · APRICITY THERAPEUTICS, INC. · 2020 · $168,000

## Abstract

Drug Transporters in Farm Animals
Membrane transporters in the ATP Binding Cassette Family (ABC) play critical roles in cellular efflux of
endogenous metabolites as well as xenobiotics including prescription drugs. A key ABC transporter gene that
is present in mammals and other species is ABCB1, which encodes P-glycoprotein (P-gp). Highly expressed
in environment-organism barrier tissues such as the intestine, P-gp represents a major impediment to drug
absorption limiting the oral bioavailability of its substrates. Accordingly, candidate drugs are screened for their
interactions with human P-gp and those with limited or no interactions with P-gp are generally selected for
further development. However, P-gp from various mammalian species has been shown to have profound
differences in its substrate and inhibitor specificities. Though human P-gp expressing cell lines are available for
screening during drug development, currently, cell lines expressing farm animal P-gps are not available.
Therefore, companies that are developing drugs to treat animals and in particular farm animals, must rely on
cells expressing human P-gp to predict drugs to take forward in costly drug development efforts. The overall
goals of this Phase I SBIR research proposal is to create and characterize cell lines stably expressing
farm animal P-gps including those from chicken, pig, sheep and cattle. The cell lines will serve as a
resource for drug developers to predict the absorption of candidate drugs. A secondary goal is to create
and validate a transformed yeast strain expressing human P-gp for use in testing food additives and
contaminants in animal feed as potential inhibitors of human P-gp. Two aims are proposed. In aim 1, we will
create stable cell lines expressing P-gp from the various farm animals and characterize the interactions of
canonical substrates and inhibitors of human P-gp with the various animal P-gps. In aim 2, we will transform
yeast with human P-gp (ABCB1) and create a robust assay to use in testing feed contaminants and additives
for their ability to inhibit human P-gp and cause potential toxicities to people ingesting animal products.
Methods used in the proposed studies include new technologies for creation of cell lines stably expressing the
transporter orthologs, fluorescent and isotopic uptake and flux assays in cells, as well as yeast genetics,
transformation protocols and cytotoxicity assays. Overall these studies will lead to a set of new tools that can
be used in the development and repurposing of drugs for the treatment of diseases of farm animals, and the
assessment of ingredients or contaminants in feed for potentially toxic effects on human P-gp.

## Key facts

- **NIH application ID:** 10080478
- **Project number:** 1R43FD006909-01
- **Recipient organization:** APRICITY THERAPEUTICS, INC.
- **Principal Investigator:** Claire Brett
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2020
- **Award amount:** $168,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080478

## Citation

> US National Institutes of Health, RePORTER application 10080478, Drug Transporters in Farm Animals (1R43FD006909-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10080478. Licensed CC0.

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