ArticlePharmaceutical research2013
Identification of novel activators of constitutive androstane receptor from FDA-approved drugs by integrated computational and biological approaches.
Article in Pharmaceutical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 47 citations in OpenAlex.
- ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.Pharmacological reviews · 2023Review
- Discovery of Novel Human Constitutive Androstane Receptor Agonists with the Imidazo[1,2-Journal of medicinal chemistry · 2023Article
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Targeting CAR and Nrf2 improves cyclophosphamide bioactivation while reducing doxorubicin-induced cardiotoxicity in triple-negative breast cancer treatment.JCI insight · 2022Article
- Transporter Gene Regulation in Sandwich Cultured Human Hepatocytes Through the Activation of Constitutive Androstane Receptor (CAR) or Aryl Hydrocarbon Receptor (AhR).Frontiers in pharmacology · 2020Article
- High-content analysis of constitutive androstane receptor (CAR) translocation identifies mosapride citrate as a CAR agonist that represses gluconeogenesis.Biochemical pharmacology · 2019Article
- Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies.European journal of medicinal chemistry · 2019Article
- DL5050, a Selective Agonist for the Human Constitutive Androstane Receptor.ACS medicinal chemistry letters · 2019Article
- Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space.ACS central science · 2018Article
- Teriflunomide Is an Indirect Human Constitutive Androstane Receptor (CAR) Activator Interacting With Epidermal Growth Factor (EGF) Signaling.Frontiers in pharmacology · 2018Article
- Mechanisms of xenobiotic receptor activation: Direct vs. indirect.Biochimica et biophysica acta · 2016Review
- 1001 Ways to run AutoDock Vina for virtual screening.Journal of computer-aided molecular design · 2016Article
- Genome-wide analysis of human constitutive androstane receptor (CAR) transcriptome in wild-type and CAR-knockout HepaRG cells.Biochemical pharmacology · 2015Article
- Combinatorial Pharmacophore-Based 3D-QSAR Analysis and Virtual Screening of FGFR1 Inhibitors.International journal of molecular sciences · 2015Article
- Quantitative high-throughput identification of drugs as modulators of human constitutive androstane receptor.Scientific reports · 2015Article
- Targeting xenobiotic receptors PXR and CAR in human diseases.Drug discovery today · 2015Review
- Activation of the constitutive androstane receptor inhibits gluconeogenesis without affecting lipogenesis or fatty acid synthesis in human hepatocytes.Toxicology and applied pharmacology · 2014Article
- Pathway analysis for drug repositioning based on public database mining.Journal of chemical information and modeling · 2014Article
- Pharmacophore and 3D-QSAR characterization of 6-arylquinazolin-4-amines as Cdc2-like kinase 4 (Clk4) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) inhibitors.Journal of chemical information and modeling · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe constitutive androstane receptor (CAR, NR1I3) is a xenobiotic sensor governing the transcription of numerous hepatic genes associated with drug metabolism and clearance. Recent evidence suggests that CAR also modulates energy homeostasis and cancer development. Thus, identification of novel human (h) CAR activators is of both clinical importance and scientific interest.
methodsDocking and ligand-based structure-activity models were used for virtual screening of a database containing over 2000 FDA-approved drugs. Identified lead compounds were evaluated in cell-based reporter assays to determine hCAR activation. Potential activators were further tested in human primary hepatocytes (HPHs) for the expression of the prototypical hCAR target gene CYP2B6.
resultsNineteen lead compounds with optimal modeling parameters were selected for biological evaluation. Seven of the 19 leads exhibited moderate to potent activation of hCAR. Five out of the seven compounds translocated hCAR from the cytoplasm to the nucleus of HPHs in a concentration-dependent manner. These compounds also induce the expression of CYP2B6 in HPHs with rank-order of efficacies closely resembling that of hCAR activation.
conclusionThese results indicate that our strategically integrated approaches are effective in the identification of novel hCAR modulators, which may function as valuable research tools or potential therapeutic molecules.
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