ArticleMolecular pharmacology2013
Effects on gene expression in rat liver after administration of RXR agonists: UAB30, 4-methyl-UAB30, and Targretin (Bexarotene).
Article in Molecular pharmacology, 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers.Cancer prevention research (Philadelphia, Pa.) · 2019Trial
- Retinoid X Receptor agonists as selective modulators of the immune system for the treatment of cancer.Pharmacology & therapeutics · 2023Review
- Next-generation retinoid X receptor agonists increase ATRA signaling in organotypic epithelium cultures and have distinct effects on receptor dynamics.The Journal of biological chemistry · 2023Article
- Conformationally Defined Rexinoids for the Prevention of Inflammation and Nonmelanoma Skin Cancers.Journal of medicinal chemistry · 2022Article
- 9-cis-UAB30, a novel rexinoid agonist, decreases tumorigenicity and cancer cell stemness of human neuroblastoma patient-derived xenografts.Translational oncology · 2021Article
- The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer.Scientific reports · 2020Article
- Novel retinoic acid derivative induces differentiation and growth arrest in neuroblastoma.Journal of pediatric surgery · 2020Article
- UAB30, A Novel Rexinoid Agonist, Decreases Stemness In Group 3 Medulloblastoma Human Cell Line Xenografts.Translational oncology · 2019Article
- UAB30, a novel RXR agonist, decreases tumorigenesis and leptomeningeal disease in group 3 medulloblastoma patient-derived xenografts.Journal of neuro-oncology · 2018Article
- Screening of Chemopreventive Agents in Animal Models: Results on Reproducibility, Agents of a Given Class, and Agents Tested During Tumor Progression.Cancer prevention research (Philadelphia, Pa.) · 2018Review
- The retinoid X receptor agonist, 9-cis UAB30, inhibits cutaneous T-cell lymphoma proliferation through the SKP2-p27kip1 axis.Journal of dermatological science · 2018Article
- Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.Current topics in medicinal chemistry · 2017Review
- Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies.Molecular cancer therapeutics · 2016Article
- Retinoids and rexinoids in cancer prevention: from laboratory to clinic.Seminars in oncology · 2016Review
- Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.PloS one · 2016Article
- Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers.Journal of medicinal chemistry · 2015Article
- Methyl substitution of a rexinoid agonist improves potency and reveals site of lipid toxicity.Journal of medicinal chemistry · 2014Article
- Defining the communication between agonist and coactivator binding in the retinoid X receptor α ligand binding domain.The Journal of biological chemistry · 2014Article
- Methyl-substituted conformationally constrained rexinoid agonists for the retinoid X receptors demonstrate improved efficacy for cancer therapy and prevention.Bioorganic & medicinal chemistry · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Examination of three retinoid X receptor (RXR) agonists [Targretin (TRG), UAB30, and 4-methyl-UAB30 (4-Me-UAB30)] showed that all inhibited mammary cancer in rodents and two (TRG and 4-Me-UAB30) strikingly increased serum triglyceride levels. Agents were administered in diets to female Sprague-Dawley rats. Liver RNA was isolated and microarrayed on the Affymetrix GeneChip Rat Exon 1.0 ST array. Statistical tests identified genes that exhibited differential expression and fell into groups, or modules, with differential expression among agonists. Genes in specific modules were changed by one, two, or all three agonists. An interactome analysis assessed the effects on genes that heterodimerize with known nuclear receptors. For proliferator-activated receptor α/RXR-activated genes, the strongest response was TRG > 4-Me-UAB30 > UAB30. Many liver X receptor/RXR-related genes (e.g., Scd-1 and Srebf1, which are associated with increased triglycerides) were highly expressed in TRG and 4-Me-UAB30- but not UAB30-treated livers. Minimal expression changes were associated with retinoic acid receptor or vitamin D receptor heterodimers by any of the agonists. UAB30 unexpectedly and uniquely activated genes associated with the aryl hydrocarbon hydroxylase (Ah) receptor (Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1). Based on the Ah receptor activation, UAB30 was tested for its ability to prevent dimethylbenzanthracene (DMBA)-induced mammary cancers, presumably by inhibiting DMBA activation, and was highly effective. Gene expression changes were determined by reverse transcriptase-polymerase chain reaction in rat livers treated with Targretin for 2.3, 7, and 21 days. These showed similar gene expression changes at all three time points, arguing some steady-state effect. Different patterns of gene expression among the agonists provided insight into molecular differences and allowed one to predict certain physiologic consequences of agonist treatment.
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Registered trials
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.