About

Nathan Cherrington, PhD, ATS, is an associate dean for research and a professor in the Department of Pharmacology and Toxicology at the University of Arizona. He directs the NIEHS P30 Southwest Environmental Health Sciences Center and the NIEHS T32 Training in Environmental Toxicology of Human Disease. Additionally, he serves as the interim director for the College's Center for Toxicology and holds joint appointments as a professor in Clinical Translation Services and in the Mel & Enid Zuckerman College of Public Health. Dr. Cherrington has authored more than 200 journal articles and abstracts focusing on drug metabolism and disposition, especially related to liver damage. His research areas include adverse drug reactions, drug metabolism and distribution, gene expression and polymorphisms, phenoconversion, hepatic and renal ontogeny, and non-alcoholic steatohepatitis. He has received numerous awards, including the Best Paper Award and the SOT Paper of the Year from the Society of Toxicology, and holds two patents. Dr. Cherrington is a fellow of the Academy of Toxicological Sciences and is actively involved in professional organizations such as the Society of Toxicology and the American Society for Pharmacology and Experimental Therapeutics.

Research topics

• Biochemistry
• Biology
• Chemistry
• Molecular biology
• Pharmacology
• Virology
• Cell biology
• Stereochemistry
• Immunology
• Endocrinology
• Microbiology

Selected publications

• Experimental and computational approaches for evaluating molecule interactions with equilibrative nucleoside transporters 1 and 2

  Journal of Pharmacology and Experimental Therapeutics · 2025-07-16 · 2 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• ToxPoint: The case for Equilibrative Nucleoside Transporters in current regulatory guidance

  Toxicological Sciences · 2025-09-02 · 1 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Computational Approaches for Predicting Drug Interactions with Human Organic Anion Transporter 4 (OAT4)

  Molecular Pharmaceutics · 2025-03-20 · 4 citations

  articleOpen accessSenior authorCorresponding

  Human Organic Anion Transporter 4 (OAT4) is predominantly expressed in the kidneys, particularly in the apical membrane of the proximal tubule cells. This transporter is involved in the renal handling of endogenous and exogenous organic anions (OAs), making it an important transporter for drug–drug interactions (DDIs). To better understand OAT4-compound interactions, we generated single concentration (25 μM) in vitro inhibition data for over 1400 small molecules against the uptake of the fluorescent OA 6-carboxyfluorescein (6-CF) in Chinese hamster ovary (CHO) cells. Several drugs exhibiting higher than 50% inhibition in this initial screen were selected to determine IC50 values against three structurally distinct OAT4 substrates: estrone sulfate (ES), ochratoxin A (OTA), and 6-CF. These IC50 values were then compared to the drug plasma concentration as per the 2020 FDA drug–drug interaction (DDI) guidance. Several screened compounds, including some not previously reported, emerged as novel inhibitors of OAT4. These data were also used to build machine learning classification models to predict the activity of potential OAT4 inhibitors. We compared multiple machine learning algorithms and data cleaning techniques to model these screening data and investigated the utility of conformal predictors to predict OAT4 inhibition of a leave-out set. These experimental and computational approaches allowed us to model diverse and unbalanced data to enable predictions for DDIs mediated by this transporter.

  PublisherOA PDFDOI

• Inhibition of equilibrative nucleoside transporters 1 and 2 by proteolysis-targeting chimeras (PROTACs)

  Journal of Pharmacology and Experimental Therapeutics · 2025-12-01 · 2 citations

  article
  PublisherDOI

• Characterization of Human Organic Anion Transporter 4 (hOAT4) and Mouse Oat5 (mOat5) As Functional Orthologs for Renal Anion Uptake and Efflux Transport

  Journal of Pharmacology and Experimental Therapeutics · 2024-04-16 · 6 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Drug Transporters at the Human Blood-Testis Barrier

  Drug Metabolism and Disposition · 2023-02-02 · 20 citations

  reviewOpen accessSenior author
  PublisherOA PDFDOI

• Transporter Inhibition Profile for the Antivirals Tilorone, Quinacrine and Pyronaridine

  ACS Omega · 2023-03-24 · 3 citations

  articleOpen access

  efficacy against SARS-CoV-2 in mice. We have recently tested these molecules and other antivirals against human organic cation transporters (OCTs) and apical multidrug and toxin extruders (MATEs). Quinacrine was found to be an inhibitor of OCT2, while tilorone and pyronaridine were less potent, and these displayed variability depending on the substrate used. To assess whether any of these three molecules have other potential interactions with additional transporters, we have now screened them at 10 μM against various human efflux and uptake transporters including P-gp, OATP1B3, OAT1, OAT3, MRP1, MRP2, MRP3, BCRP, as well as confirmational testing against OCT1, OCT2, MATE1 and MATE2K. Interestingly, in this study tilorone appears to be a more potent inhibitor of OCT1 and OCT2 than pyronaridine or quinacrine. However, both pyronaridine and quinacrine appear to be more potent inhibitors of MATE1 and MATE2K. None of the three compounds inhibited MRP1, MRP2, MRP3, OAT1, OAT3, P-gp or OATP1B3. Similarly, we previously showed that tilorone and pyronaridine do not inhibit OATP1B1 and have confirmed that quinacrine behaves similarly. In total, these observations suggest that the three compounds only appear to interact with OCTs and MATEs to differing extents, suggesting they may be involved in fewer clinically relevant drug-transporter interactions involving pharmaceutical substrates of the other major transporters tested.

  PublisherDOI

• Representative Rodent Models for Renal Transporter Alterations in Human Nonalcoholic Steatohepatitis

  Drug Metabolism and Disposition · 2023-05-03 · 3 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Addressing the Clinical Importance of Equilibrative Nucleoside Transporters in Drug Discovery and Development

  Clinical Pharmacology & Therapeutics · 2023-07-05 · 17 citations

  reviewOpen accessSenior authorCorresponding

  The US Food and Drug Administration (FDA), European Medicines Agency (EMA), and Pharmaceuticals and Medical Devices Agency (PMDA) guidances on small-molecule drug-drug interactions (DDIs), with input from the International Transporter Consortium (ITC), recommend the evaluation of nine drug transporters. Although other clinically relevant drug uptake and efflux transporters have been discussed in ITC white papers, they have been excluded from further recommendation by the ITC and are not included in current regulatory guidances. These include the ubiquitously expressed equilibrative nucleoside transporters (ENT) 1 and ENT2, which have been recognized by the ITC for their potential role in clinically relevant nucleoside analog drug interactions for patients with cancer. Although there is comparatively limited clinical evidence supporting their role in DDI risk or other adverse drug reactions (ADRs) compared with the nine highlighted transporters, several in vitro and in vivo studies have identified ENT interactions with non-nucleoside/non-nucleotide drugs, in addition to nucleoside/nucleotide analogs. Some noteworthy examples of compounds that interact with ENTs include cannabidiol and selected protein kinase inhibitors, as well as the nucleoside analogs remdesivir, EIDD-1931, gemcitabine, and fialuridine. Consequently, DDIs involving the ENTs may be responsible for therapeutic inefficacy or off-target toxicity. Evidence suggests that ENT1 and ENT2 should be considered as transporters potentially involved in clinically relevant DDIs and ADRs, thereby warranting further investigation and regulatory consideration.

  PublisherOA PDFDOI

• Excretion of polybrominated diphenyl ethers and AhR activation in breastmilk among firefighters

  Toxicological Sciences · 2023-02-28 · 6 citations

  articleOpen access

  Excretion of toxicants accumulated from firefighter exposures through breastmilk represents a potential hazard. We investigated if firefighting exposures could increase the concentration of polybrominated diphenyl ethers (PBDEs) and aryl hydrocarbon receptor (AhR) activation in excreted breastmilk. Firefighters and nonfirefighters collected breastmilk samples prior to any firefighting responses (baseline) and at 2, 8, 24, 48, and 72 h after a structural fire (firefighters only). Five PBDE analytes (BDEs 15, 28, 47, 99, and 153) detected in at least 90% of samples were summed for analyses. The AhR in vitro DR CALUX bioassay assessed the mixture of dioxin-like compounds and toxicity from breastmilk extracts. Baseline PBDEs and AhR responses were compared between firefighters and nonfirefighters. Separate linear mixed models assessed changes in sum of PBDEs and AhR response among firefighters over time and effect modification by interior or exterior response was assessed. Baseline PBDE concentrations and AhR responses did not differ between the 21 firefighters and 10 nonfirefighters. There were no significant changes in sum of PBDEs or AhR response among firefighters over time postfire, and no variation by interior or exterior response. Plots of sum of PBDEs and AhR response over time demonstrated individual variation but no consistent pattern. Currently, our novel study results do not support forgoing breastfeeding after a fire exposure. However, given study limitations and the potential hazard of accumulated toxicants from firefighter exposures excreted via breastfeeding, future studies should consider additional contaminants and measures of toxicity by which firefighting may impact maternal and child health.

  PublisherOA PDFDOI

Recent grants

• Pediatric Adverse Drug Reactions in NASH

  NIH · $1.6M · 2010–2016

• NIH Grant K22ES011646

  NIH · $324k · 2007

• Circumventing the Blood-Testis Barrier

  NIH · $1.2M · 2017–2021

• NIH Grant R01DK068039

  NIH · $1.5M · 2011

• NIH Grant F32ES005883

  NIH · $55k

Frequent coauthors

• José E. Manautou

  University of Connecticut

  83 shared

• John Clarke

  Washington State University Spokane

  66 shared

• Rhiannon N. Hardwick

  Bristol-Myers Squibb (United States)

  64 shared

• Mark J. Canet

  Denali Therapeutics (United States)

  63 shared

• Angela L. Slitt

  University of Rhode Island

  61 shared

• Lauren M. Aleksunes

  Environmental and Occupational Health Sciences Institute

  51 shared

• George L. Scheffer

  46 shared

• Stephen H. Wright

  43 shared

Awards & honors

• 1885 Society Distinguished Scholar
• Fellow, Academy of Toxicological Sciences
• Best Paper Award Society of Toxicology, Spring 2024
• SOT Paper of the Year Society of Toxicology, Spring 2024