ArticleMolecular pharmacology2014
In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo.
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Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31citing papers in PubMed
3.1field-weighted citation impact, top 10% of its field
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Aryl hydrocarbon receptor pharmacology-mechanisms, ligands, and therapeutic potential.Pharmacological reviews · 2026Review
- Exploration of Agonist and Antagonist Binding Sites within the Cytosolic AHR Complex Using Molecular Modeling.ACS omega · 2026Article
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- Drug-Induced Glucose Metabolism Disorders: Role of Aryl Hydrocarbon Receptor.Journal of xenobiotics · 2025Review
- Tryptophan metabolism: From physiological functions to key roles and therapeutic targets in cancer (Review).Oncology reports · 2025Review
- Review
- Article
- Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review).Molecular medicine reports · 2024Review
- Aryl Hydrocarbon Receptor as an Anticancer Target: An Overview of Ten Years Odyssey.Molecules (Basel, Switzerland) · 2023Review
- Review
- Article
- Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.Journal of molecular medicine (Berlin, Germany) · 2022Review
- The aryl hydrocarbon receptor as a model PAS sensor.Toxicology reports · 2022Review
- Targeting Tryptophan Catabolism in Cancer Immunotherapy Era: Challenges and Perspectives.Frontiers in immunology · 2022Review
- Review ofFrontiers in endocrinology · 2022Review
- Recent advances in the development of AHR antagonists in immuno-oncology.RSC medicinal chemistry · 2021Review
- Uraemic solutes as therapeutic targets in CKD-associated cardiovascular disease.Nature reviews. Nephrology · 2021Review
- AhR and Cancer: From Gene Profiling to Targeted Therapy.International journal of molecular sciences · 2021Review
- AhR Ligands Modulate the Differentiation of Innate Lymphoid Cells and T Helper Cell Subsets That Control the Severity of a Pulmonary Fungal Infection.Frontiers in immunology · 2021Article
- How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Ashley J ParksMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Michael P PollastriMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Mark E HahnMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Elizabeth A StanfordMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Olga NovikovMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Diana G FranksMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Sarah E HaighMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Supraja NarasimhanMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Trent D AshtonMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Timothy G HopperMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Dmytro KozakovMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Dimitri BeglovMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Sandor VajdaMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
Jennifer J SchlezingerMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.).
David H SherrMolecular Medicine Program, Boston University School of Medicine, Boston, Massachusetts (A.J.P., E.A.S., O.N.); Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts (A.J.P., E.A.S., O.N., S.N., J.J.S., DHS); Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts (M.P.P., T.G.H.); Department of Chemistry, Boston University (T.D.A.); Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts (M.E.H., D.G.F.); Wake Forest Innovations, Wake Forest University, Winston-Salem, North Carolina (S.E.H.); and Biomedical Engineering, Boston University, Boston, Massachusetts (D.K., D.B., S.V.) dsherr@bu.edu.
Boston University · USWake Forest University · USNortheastern University · USWoods Hole Oceanographic Institution · US
Funding
Training CoreP42ES007381 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI MONTI, STEFANO · 1995 to 2019
$46.1MSignaling Pathways in Stages of TumorigenesisP01ES011624 · NIEHS · TUFTS UNIVERSITY BOSTON · PI SONENSHEIN, GAIL E. · 2001 to 2012
$11.4MRESEARCH TRAINING IN BLOOD DISEASES AND RESOURCEST32HL007501 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI LERNER, ADAM, STEINBERG, MARTIN H. · 1985 to 2018
$5.4MComputational mapping of proteins for the binding of ligandsR01GM064700 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI VAJDA, SANDOR · 2003 to 2015
$4.3MAHR Signaling in Mammalian and Non-Mammalian ModelsR01ES006272 · NIEHS · WOODS HOLE OCEANOGRAPHIC INSTITUTION · PI HAHN, MARK E · 1999 to 2014
$4.1MNHLBI NIH HHS T32 HL007501NIEHS NIH HHS P01 ES011624NIEHS NIH HHS P42 ES007381NIEHS NIH HHS P42-ES007381NIEHS NIH HHS R01 ES006272NIEHS NIH HHS R01-ES006272NIEHS NIH HHS R01-ES11624NIGMS NIH HHS R01 GM064700NIGMS NIH HHS R01-GM064700
Abstract
The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of targeted therapeutics. Here, ligand shape-based virtual modeling techniques were used to identify novel AHR ligands on the basis of previously identified chemotypes. Four structurally unique compounds were identified. One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (CB7993113), was further tested for its ability to block three AHR-dependent biologic activities: triple-negative breast cancer cell invasion or migration in vitro and AHR ligand-induced bone marrow toxicity in vivo. CB7993113 directly bound both murine and human AHR and inhibited polycyclic aromatic hydrocarbon (PAH)- and TCDD-induced reporter activity by 75% and 90% respectively. A novel homology model, comprehensive agonist and inhibitor titration experiments, and AHR localization studies were consistent with competitive antagonism and blockade of nuclear translocation as the primary mechanism of action. CB7993113 (IC50 3.3 × 10(-7) M) effectively reduced invasion of human breast cancer cells in three-dimensional cultures and blocked tumor cell migration in two-dimensional cultures without significantly affecting cell viability or proliferation. Finally, CB7993113 effectively inhibited the bone marrow ablative effects of 7,12-dimethylbenz[a]anthracene in vivo, demonstrating drug absorption and tissue distribution leading to pharmacological efficacy. These experiments suggest that AHR antagonists such as CB7993113 may represent a new class of targeted therapeutics for immunomodulation and/or cancer therapy.
Indexed as
AnimalsBiological FactorsBone Marrow CellsCell LineCell Line, TumorCell MovementCell ProliferationChlorocebus aethiopsCOS CellsHumansLigandsMaleMiceMice, Inbred C57BLReceptors, Aryl HydrocarbonStromal CellsBiological FactorsLigandsReceptors, Aryl Hydrocarbon
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