ArticleBiochemistry2013
Peroxisome proliferation-activated receptor δ agonist GW0742 interacts weakly with multiple nuclear receptors, including the vitamin D receptor.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- PPARβ/δ Agonist GW0742 Modulates Microglial and Astroglial Gene Expression in a Rat Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2024Article
- Co-Incubation with PPARβ/δ Agonists and Antagonists Modeled Using Computational Chemistry: Effect on LPS Induced Inflammatory Markers in Pulmonary Artery.International journal of molecular sciences · 2021Article
- The role of peroxisome proliferator-activated receptors (PPAR) in immune responses.Metabolism: clinical and experimental · 2021Review
- Alternative binding sites at the vitamin D receptor and their ligands.Molecular and cellular endocrinology · 2019Review
- Novel VDR antagonists based on the GW0742 scaffold.Bioorganic & medicinal chemistry letters · 2018Article
- Parallel Chemistry Approach to Identify Novel Nuclear Receptor Ligands Based on the GW0742 Scaffold.ACS combinatorial science · 2017Article
- Fluorescence polarization assays in high-throughput screening and drug discovery: a review.Methods and applications in fluorescence · 2016Article
- Inhibitors for the Vitamin D Receptor-Coregulator Interaction.Vitamins and hormones · 2016Review
- Regulation of the orexigenic neuropeptide, enkephalin, by PPARδ and fatty acids in neurons of the hypothalamus and forebrain.Journal of neurochemistry · 2015Article
- Anticancer activity of VDR-coregulator inhibitor PS121912.Cancer chemotherapy and pharmacology · 2014Article
- Activation of peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) inhibits human breast cancer cell line tumorigenicity.Molecular cancer therapeutics · 2014Article
- Development of novel Vitamin D Receptor-Coactivator Inhibitors.ACS medicinal chemistry letters · 2014Article
- IDENTIFICATION OF VDR ANTAGONISTS AMONG NUCLEAR RECEPTOR LIGANDS USING VIRTUAL SCREENING.Nuclear receptor research · 2014Article
- Modulation of Transcription mediated by the Vitamin D Receptor and the Peroxisome Proliferator-Activated Receptor δ in the presence of GW0742 analogs.Journal of biomolecular research & therapeutics · 2014Article
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
A high-throughput screening campaign was conducted to identify small molecules with the ability to inhibit the interaction between the vitamin D receptor (VDR) and steroid receptor coactivator 2. These inhibitors represent novel molecular probes for modulating gene regulation mediated by VDR. Peroxisome proliferator-activated receptor (PPAR) δ agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pan nuclear receptor antagonist at concentrations of > 12.1 μM. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor. Surprisingly, GW0742 behaved as a PPAR agonist and antagonist, activating transcription at lower concentrations and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742 increased the fluorescence intensity and level of fluorescence polarization at an excitation wavelength of 595 nm and an emission wavelength of 615 nm in a dose-dependent manner. The GW0742-inhibited NR-coactivator binding resulted in a reduced level of expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3, and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.