更新于：2024-11-01

RARs x PXR

更新于：2024-11-01

基本信息

关联

项与 RARs x PXR 相关的药物

Vitamin A/Vitamin E

维生素A/维生素E

靶点

PXR x RARs

作用机制

PXR激动剂 [+1]

在研机构-

原研机构-

在研适应症

维生素a缺乏症 [+1]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区-

首次获批日期1800-01-20

Ascorbic Acid/Biotin/Cyanocobalamin/Dexpanthenol/Ergocalciferol/Folic Acid/Niacinamide/Pyridoxine Hydrochloride/Riboflavin 5'-Phosphate Sodium/ Thiamine Hydrochloride/Vitamin A/Vitamin E

抗坏血酸/生物素/氰钴胺/右旋泛醇/麦角钙化醇/叶酸/烟酰胺/盐酸吡哆醇/核黄素5’-磷酸钠/盐酸亚硫胺/维生素A/维生素E

靶点

叶酸受体 x MUT x PXR x RARs x VDR x mAChRs

作用机制

叶酸受体调节剂 [+7]

在研机构-

原研机构

Watson Laboratories, Inc.

在研适应症-

非在研适应症

膳食补充剂

最高研发阶段撤市

首次获批国家/地区

美国

首次获批日期1982-07-13

100 项与 RARs x PXR 相关的临床结果

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100 项与 RARs x PXR 相关的转化医学

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0 项与 RARs x PXR 相关的专利（医药）

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项与 RARs x PXR 相关的文献（医药）

2023-10-01·Current Pharmaceutical Biotechnology

Roles of Nuclear Receptors in Esophageal Cancer

Review

作者: Chen, Wei-Dong ; Liu, Jiaxuan ; Deng, Lihao ; Wang, Yan-Dong

Background:Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression.Objectives:NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC.Methods:This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments.Results:NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC.Conclusion:The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases.

2021-01-01·Ecotoxicology and Environmental Safety2区 · 环境科学与生态学

Interaction of BDE-47 with nuclear receptors (NRs) based on the cytotoxicity: In vitro investigation and molecular interaction

2区 · 环境科学与生态学

Article

作者: Song, Jiayi ; Zhang, Jianqing ; Zhou, Qunfang ; Zhao, Chunyan ; Li, Yunxiu

Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting chemicals that possess neuroendocrine and reproductive toxicity to humans and disturb thyroid hormone homeostasis, neurobehavior, and development. The most predominant congener of PBDEs in humans and other organisms is 2,2',4,4'-tetrabromodiphenyl ether (BDE-47); however, the molecular mechanisms underlying its cytotoxicity remain largely unknown. Here, we evaluated the toxic effect and underlying mechanism of nuclear receptors (NRs) induced by BDE-47 in SK-N-SH human neuroblastoma cells. The CCK-8 cell viability assay showed that the proliferation of human SK-N-SH cells exposed to BDE-47 was significantly inhibited in time- and dose-dependent manners, and flow cytometry showed that cell cycle was arrested at the S phase after BDE-47 exposure. Moreover, compared with the control group, the expression of retinoic acid receptor alpha (RXRα), pregnane X receptor (PXR), thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors (PPARs) at the mRNA and protein levels was significantly increased, as determined by quantitative PCR and western blot analysis, demonstrating that BDE-47 activated the NRs in vitro. Moreover, BDE-47 could bind to all four NRs in the affinity order of PPARγ > PXR > TRβ > RXRα under molecular dynamics. Because RXR is the promiscuous dimerization partner for a large number of NRs, ZDock was used to calculate its interaction with other three NRs. Taking the number of hydrogen bonds and ZDock scores into account, the rank of docking ability between RXRα and the NRs was PXR > TRβ > PPARγ. Further analysis of the interaction between BDE-47 and dimerized-NRs, the affinity order was RXRα > TRβ > PXR > PPARγ via Glide. The results of this study demonstrated that BDE-47 interfered the cross-talk among NRs, especially the promiscuous RXRα, which might be critical for the harmonized re-adjustment of cytotoxicity and biological regulation. Our findings provide a better understanding of the mechanisms underlying toxic effects and intermolecular interaction induced by BDE-47.

2020-02-01·Toxicology in Vitro3区 · 医学

Activation of human nuclear receptors by perfluoroalkylated substances (PFAS)

3区 · 医学

Article

作者: Buhrke, Thorsten ; Behr, Anne-Cathrin ; Plinsch, Christin ; Braeuning, Albert

Perfluoralkylated substances (PFAS) such as perfluorooctanoic acid (PFOA) or perfluorooctanesulfonic acid (PFOS) are used to produce, e.g., surface coatings with water- and dirt-repellent properties. These substances have been shown to be hepatotoxic in rodents, and the mechanism of action is mostly attributed to the PFAS-mediated activation of the peroxisome proliferator-activated receptor alpha (PPARα). In the present study, we investigated by using luciferase-based reporter gene assays whether PFOA, PFOS and six alternative PFAS can activate, in addition to PPARα, eight other human nuclear receptors. All tested PFAS except for perfluorobutanesulfonic acid (PFBS) were able to activate human PPARα. Perfluoro-2-methyl-3-oxahexanoic acid (PMOH) and 3H-perfluoro-3-[(3-methoxypropoxy) propanoic acid] (PMPP) were weak agonists of human PPARγ. The other human nuclear receptors (PPARδ, CAR, PXR, FXR, LXRα, RXRα and RARα) were not affected by any PFAS tested in this study. Although PMOH was more effective than PFOA in stimulating PPARα in the transactivation assay, it was less effective in stimulating PPARα-dependent target gene expression in human HepG2 hepatocarcinoma cells. Notably, any effect observed in this in vitro study only occurred at concentrations higher than 10 μM of the respective PFAS which is in all cases several magnitudes above the average blood concentration in the Western population. Thus, the results suggest that nuclear receptor activation may only play a minor role in potential PFAS-mediated adverse effects in humans.