更新于：2024-05-01

RARβ2

维甲酸受体β

更新于：2024-05-01

基本信息

别名

HAP、HBV-activated protein、NR1B2

+ [8]

简介

Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (PubMed:12554770). The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element (PubMed:29021580). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).

关联

项与 RARβ2 相关的药物

Benzoyl Peroxide/Tretinoin

过氧苯甲酰/维A酸

靶点

RARα x RARβ2 x RARγ

作用机制

RARα激动剂 [+2]

在研机构

GALDERMA LABORATORIES L P

原研机构

Sol-Gel Technologies Ltd.

在研适应症

寻常痤疮

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2021-07-26

Halobetasol Propionate/Tazarotene

丙酸乌倍他索/他扎罗汀

靶点

GR x RARα x RARβ2 x RARγ x cPLA2α

作用机制

GR激动剂 [+4]

在研机构

Bausch Health, Canada, Inc. [+1]

原研机构

Bausch Health Americas, Inc.

在研适应症

斑块状银屑病 [+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

美国

首次获批日期2019-04-25

Tazarotene/Betamethasone Dipropionate

他扎罗汀倍他米松

靶点

GR x RARα x RARβ2 x RARγ

作用机制

GR激动剂 [+3]

在研机构

重庆华邦制药有限公司

原研机构

重庆华邦制药有限公司

在研适应症

银屑病

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2015-03-27

147

项与 RARβ2 相关的临床试验

NCT06331624 / Recruiting临床2期

Biomarker Modulation and the Inhibition of Natural Killer Type 1 (NKT1) Cells by Oral GRI-0621 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

This is a Phase 2a, randomized, double-blind, multi-center, placebo-controlled, parallel-design, 2-arm study. Approximately 36 subjects with IPF will be randomized in a 2:1 ratio for GRI-0621 4.5mg or Placebo. GRI-0621 dose of 4.5mg will be compared with placebo following once daily oral administration for 12 weeks. Concurrently, a Sub-Study will be conducted, examining the number and activity of NKT cells in BAL, for up to 12 eligible subjects (across various centers). An interim analysis will be performed when 24 subjects complete 6 weeks of treatment (approximately 8 placebo subjects).

开始日期2024-03-01

申办/合作机构

GRI Bio Operations, Inc.

CTRI/2023/11/060308 / Not yet recruitingN/A

Comparative efficacy of different concentration of topical tazarotene and topical tretinoin in acne vulgaris. - NIL

开始日期2023-12-05

申办/合作机构-

CTRI/2023/10/059038 / RecruitingN/AIIT

Comparative efficacy of topical methotrexate and topical tazarotene in psoriasis vulgaris - NIL

开始日期2023-10-31

申办/合作机构

Government Medical College

100 项与 RARβ2 相关的临床结果

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100 项与 RARβ2 相关的转化医学

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0 项与 RARβ2 相关的专利（医药）

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1,904

项与 RARβ2 相关的文献（医药）

2023-12-20·Stem cell research & therapy

Competing endogenous RNA network analysis of Turner syndrome patient-specific iPSC-derived cardiomyocytes reveals dysregulation of autosomal heart development genes by altered dosages of X-inactivation escaping non-coding RNAs.

Article

作者: Yumei Luo ; Yapei Chen ; Lingxia Ge ; Guanqing Zhou ; Yaoyong Chen ; Detu Zhu

BACKGROUND:

A 45,X monosomy (Turner syndrome, TS) is the only chromosome haploinsufficiency compatible with life. Nevertheless, the surviving TS patients still suffer from increased morbidity and mortality, with around one-third of them subjecting to heart abnormalities. How loss of one X chromosome drive these conditions remains largely unknown.

METHODS:

Here, we have generated cardiomyocytes (CMs) from wild-type and TS patient-specific induced pluripotent stem cells and profiled the mRNA, lncRNA and circRNA expression in these cells.

RESULTS:

We observed lower beating frequencies and higher mitochondrial DNA copies per nucleus in TS-CMs. Moreover, we have identified a global transcriptome dysregulation of both coding and non-coding RNAs in TS-CMs. The differentially expressed mRNAs were enriched of heart development genes. Further competing endogenous RNA network analysis revealed putative regulatory circuit of autosomal genes relevant with mitochondrial respiratory chain and heart development, such as COQ10A, RARB and WNT2, mediated by X-inactivation escaping lnc/circRNAs, such as lnc-KDM5C-4:1, hsa_circ_0090421 and hsa_circ_0090392. The aberrant expressions of these genes in TS-CMs were verified by qPCR. Further knockdown of lnc-KDM5C-4:1 in wild-type CMs exhibited significantly reduced beating frequencies.

CONCLUSIONS:

Our study has revealed a genomewide ripple effect of X chromosome halpoinsufficiency at post-transcriptional level and provided insights into the molecular mechanisms underlying heart abnormalities in TS patients.

2023-12-01·Environmental science & technology

Unregistered Hexaphenoxycyclotriphosphazene and Its Metabolite Antagonize Retinoic Acid and Retinoic X Receptors and Cause Early Developmental Damage.

Article

作者: Feifan Wu ; Ruichao Chen ; Yu Li ; Yi Wan ; Jianying Hu

Hexaphenoxycyclotriphosphazene (HPCTP), an unregistered chemical, has been used as a substitute for triphenyl phosphate in flame retardants and plasticizers. Here, we identified its metabolite, pentaphenoxycyclotriphosphazene (PPCTP) in the liver of Japanese medaka exposed to HPCTP. When sexually mature female medaka were exposed to HPCTP at 37.0, 90.4, and 465.4 ng/L for 35 days, the HPCTP concentration (642.1-2531.9 ng/g lipid weight [lw]) in the embryos considerably exceeded that (34.7-298.1 ng/g lw) in the maternal muscle, indicating remarkable maternal transfer. During 0-9 days postfertilization, the HPCTP concentration in the embryos decreased continuously, while the PPCTP concentration increased. HPCTP and PPCTP antagonized the retinoic X receptor with 50% inhibitory concentrations (IC₅₀) of 34.8 and 21.2 μM, respectively, and PPCTP also antagonized the retinoic acid receptor with IC₅₀ of 2.79 μM. Such antagonistic activities may contribute to eye deformity (4.7% at 465.4 ng/L), body malformation (2.1% at 90.4 ng/L and 6.8% at 465.4 ng/L), and early developmental mortality (11.6-21.7% in all exposure groups) of the embryos. HPCTP was detected in a main tributary of the Yangtze River Basin. Thus, HPCTP poses a risk to wild fish populations, given the developmental toxicities associated with this chemical and its metabolite.

2023-11-10·International journal of cancer

Fast proliferating and slowly migrating non-small cell lung cancer cells are vulnerable to decitabine and retinoic acid combinatorial treatment.

Article

作者: Giulia Pelos ; Marisa Riester ; Jagriti Pal ; Ksenia Myacheva ; Isabelle Moneke ; John Charles Rotondo ; Michael Lübbert ; Sven Diederichs

Non-small cell lung cancer (NSCLC) patients are often elderly or unfit and thus cannot tolerate standard aggressive therapy regimes. In our study, we test the efficacy of the DNA-hypomethylating agent decitabine (DAC) in combination with all-trans retinoic acid (ATRA), which has been shown to possess little systemic adverse effects. Screening a broad panel of 56 NSCLC cell lines uncovered a decrease in cell viability after the combination treatment in 77% of the cell lines. Transcriptomics, proteomics, proliferation and migration profiling revealed that fast proliferating and slowly migrating cell lines were more sensitive to the drug combination. The comparison of mutational profiles found oncogenic KRAS mutations only in sensitive cells. Additionally, different cell lines showed a heterogeneous gene expression response to the treatment pointing to diverse mechanisms of action. Silencing KRAS, RIG-I or RARB partially reversed the sensitivity of KRAS-mutant NCI-H460 cells. To study resistance, we generated two NCI-H460 cell populations resistant to ATRA and DAC, which migrated faster and proliferated slower than the parental sensitive cells and showed signs of senescence. In summary, this comprehensive dataset uncovers a broad sensitivity of NSCLC cells to the combinatorial treatment with DAC and ATRA and indicates that migration and proliferation capacities correlate with and could thus serve as determinants for drug sensitivity in NSCLC.

项与 RARβ2 相关的新闻（医药）

2023-08-10

·Science Daily

New orally available drug for spinal cord injury found to be safe and tolerable in healthy participants

New research has demonstrated the safety and tolerability of a new drug treatment designed as a therapeutic intervention for spinal cord injury (SCI). New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has demonstrated the safety and tolerability of a new drug treatment designed as a therapeutic intervention for spinal cord injury (SCI). The research, published in British Journal of Clinical Pharmacology, found that the KCL-286 drug -- which works by activating retinoic acid receptor beta (RARb) in the spine to promote recovery -- was well tolerated by participants in a Phase 1 clinical trial, with no severe side effects. Researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI. Global prevalence of SCI is estimated to be between 0.7 and 1.2 million cases per year, with falls and road accidents being the major causes. Despite incurring a cost of $4 billion per year in direct healthcare and indirect costs (i.e. inability to work and social care) in the US alone, there are no licensed drugs that can tackle the intrinsic failure of the adult central nervous system to regenerate, and thus remains a largely unmet clinical need. Previous research by various groups has shown that nerve growth can be stimulated by activating the RARb2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARb2 agonist1, was developed by Professor Corcoran and team and used in a first in man study to test its safety in humans. 109 healthy males were divided into one of two trial groups; single ascending dose (SAD) adaptive design with a food interaction (FI) arm, and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments. SAD studies are designed to establish the safe dosage range of a medicine by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects, and measure how the medicine is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate the potential for a drug to accumulate within the body. Researchers found that participants were able to safely take 100mg doses of KCL-286, with no severe adverse events. Professor Jonathan Corcoran, Professor of Neuroscience and Director of the Neuroscience Drug Discovery Unit, at King's IoPPN and the study's senior author said, "This represents an important first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This first-in-human study has shown that a 100mg dose delivered via a pill can be safely taken by humans. Furthermore, we have also shown evidence that it engages with the correct receptor. "Our focus can hopefully now turn to researching the effects of this intervention in people with spinal cord injuries." Dr. Bia Goncalves, a senior scientist and project manager of the study, and the study's first author from King's IoPPN said, "Spinal Cord Injuries are a life changing condition that can have a huge impact on a person's ability to carry out the most basic of tasks, and the knock-on effects on their physical and mental health are significant. "The outcomes of this study demonstrate the potential for therapeutic interventions for SCI, and I am hopeful for what our future research will find." This work was possible thanks to funding from the Medical Research Council.

临床1期临床2期临床结果

2023-08-04

·生物谷

Stem Cell Rep：科学家识别出一种能激活细胞周期来增强心脏组织移植物产生的特殊分子

来自日本京都大学等机构的科学家们通过研究识别出了一种特殊分子，其或能激活细胞周期从而增强心脏组织移植物的产生。近日，一篇发表在国际杂志Stem Cell Reports上题为“Am80, a retinoic acid receptor agonist, activates the cardiomyocyte cell cycle and enhances engraftment in the heart”的研究报告中，来自日本京都大学等机构的科学家们通过研究识别出了一种特殊分子，其或能激活细胞周期从而增强心脏组织移植物的产生。研究者表示，这项研究中我们识别出了名为Am80的分子，其能激活心肌细胞的细胞周期从而就能增强心脏组织移植物的产生和植入效果；对于心脏细胞疗法而言，人类多能干细胞衍生的心肌细胞（hPSC-cardiomyocytes）在多种应用中拥有很大的前景，比如在培养皿中对心脏疾病进行建模并产生用于移植的心脏组织，然而，这些心肌细胞在移植到受损的心脏组织后往往无法存活或进行整合，从而就限制了其治疗效果。为了解决这一挑战，研究人员重点关注如何增强hPSC-心肌细胞的移植潜力，此前研究结果表明，心脏中移植细胞的生长与细胞周期密切相关，比如，心肌细胞细胞周期激活的增加与更大的移植物尺寸和心脏功能更好地改善有关；于是研究人员希望能通过探索开发新的方法来促进hPSC-心肌细胞的细胞周期激活来增强移植物在心脏细胞疗法中的性能或表现。文章中，研究人员介绍了一种基于荧光泛素化的细胞周期指示器（FUCCI，Fluorescence Ubiquitination-based Cell Cycle Indicator）系统，其是一种较为成熟的技术，能利用两种荧光融合蛋白来监测细胞周期的激活，随后研究人员将FUCCI系统应用到了人类诱导多能干细胞衍生的心肌细胞（hPSC-心肌细胞）中并测定了在心脏分化过程中细胞周期的活动情况。科学家识别出一种能激活细胞周期来增强心脏组织移植物产生的特殊分子。图片来源：Stem Cell Reports (2023). DOI:10.1016/j.stemcr.2023.06.006 通过基于FUCCI信号来分离这些细胞，研究人员还在体外发现了不同细胞周期阶段细胞中基因表达模式的差异，此外，他们还证实了hiPSC-心肌细胞在移植前的细胞周期活性或许会影响其在移植后的体内增殖潜能。利用FUCCI系统进行高通量筛选，研究人员识别出了Am80（一种视黄酸受体激动剂）或能作为一种特殊的化合物来有效激活hiPSC-心肌细胞的细胞周期；在移植前利用Am80处理hiPSC-心肌细胞的疗法或能明显增加移植物在损伤小鼠心脏中生长的尺寸或大小，这或许就表明，由视黄酸受体RARA和RARB所介导的WNT信号通路的激活或许是Am80诱导的细胞周期激活背后的特殊分子机制。研究者指出，这项研究中我们阐明了细胞周期活性和hiPSC-心肌细胞移植物尺寸及功能特性之间的关联，利用Am80，研究人员就能提供一种有效的方法来激活hiPSC-心肌细胞的细胞周期从而增加移植物的尺寸，并改善细胞移植修复受损心脏的功能结局，此外，这些研究发现或有望帮助科学家们利用hiPSC-心肌细胞来开发新型再生医学疗法，并能为研究人员阐明如何最大化其临床应用的植入潜力提供了新的见解和思路。综上，本文研究结果表明，研究人员强调了一种有效的方法来通过Am80来激活hiPSC-心肌细胞中的细胞周期，其或能作为一种新方法来增加细胞移植到受损心脏组织后的移植物尺寸或大小。（生物谷Bioon.com）原始出处： Manabu Kasamoto，Shunsuke Funakoshi，Takeshi Hatani, et al. Am80, a retinoic acid receptor agonist, activates the cardiomyocyte cell cycle and enhances engraftment in the heart, Stem Cell Reports (2023). DOI:10.1016/j.stemcr.2023.06.006