预约演示

更新于：2025-05-07

RELB

更新于：2025-05-07

基本信息

别名

I-Rel、REL-B、RELB

+ [2]

简介

NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function (PubMed:26385063).

关联

项与 RELB 相关的药物

RS-09

靶点

RELB

作用机制

RELB inhibitors

在研机构

清华大学 [+2]

原研机构

广州医科大学 [+2]

在研适应症

B细胞淋巴瘤 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

RS-47

靶点

RELB

作用机制

RELB inhibitors

在研机构

广州医科大学 [+2]

原研机构

广州医科大学 [+2]

在研适应症

B细胞淋巴瘤 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 RELB 相关的临床结果

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100 项与 RELB 相关的转化医学

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0 项与 RELB 相关的专利（医药）

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1,354

项与 RELB 相关的文献（医药）

2025-12-01·Journal of Clinical Immunology

Characteristics of Endemic Mycoses Talaromyces marneffei Infection Associated with Inborn Errors of Immunity

Review

作者: Zhang, Zhenzhen ; Liu, Cong ; Zhang, Zhiyong ; Chen, Yongwen ; An, Yunfei ; Zhang, Wenjing ; Zhao, Xiaodong ; Tang, Xuemei ; Xing, Shubin ; He, Wuyang

BACKGROUNDTalaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children.OBJECTIVEWe conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies.METHODSA systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected.RESULTSFifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals.CONCLUSIONSThe XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes.

2025-05-01·International Journal for Parasitology

Trichinella spiralis extracellular vesicles induce anti-inflammatory and regulatory immune responses in vitro

Article

作者: Tomić, Sergej ; Gruden-Movsesijan, Alisa ; Kosanović, Maja ; Sabljić, Ljiljana ; Đokić, Jelena ; Radulović, Nataša ; Glamočlija, Sofija

The helminth Trichinella spiralis, through its excretory-secretory (ES L1) products, induces immune regulatory mechanisms that modulate the host's immune response not only to itself, but also to bystander antigens, foreign or self in origin, which can result in the alleviation of inflammatory diseases. Under the influence of ES L1, dendritic cells (DCs) acquire a tolerogenic phenotype and the capacity to induce Th2 and regulatory responses. Since ES L1 products represent a complex mixture of proteins and extracellular vesicles (TsEVs) the aim of this study was to investigate the impact of TsEVs, isolated from ES L1 products, on phenotypic and functional characteristics of DCs and to elucidate whether TsEVs could reproduce the immunomodulatory effects of the complete ES L1 product. Monocyte-derived DCs treated with TsEVs acquired semi-matured phenotypes, characterized by low expression of human leukocyte antigen - DR isotype (HLA-DR), cluster of differentiation (CD) 86 (CD86), and CD40, moderate expression of CD83 and C-C chemokine receptor type 7 (CCR7), and increased expression of tolerogenic markers indoleamine 2,3-dioxygenase 1 (IDO-1) and immunoglobulin-like transcript 3 (ILT3), together with the unchanged production of IL-12 and IL-23, and elevated production of IL-10 and transforming growth factor (TGF)-β, compared with controls. Gene expression analysis of TsEV-treated DCs revealed elevated levels of mTOR, Ahr, NF-κB2, RelB, SOCS1 and SOCS3, which participate in signaling pathways involved in DC maturation and the subsequent regulation of release of both anti-inflammatory and pro-inflammatory cytokines. TsEVs promoted the capacity of DCs to drive polarization of Th2 and anti-inflammatory responses, and impaired their capacity to induce Th1/Th17 polarization. Moreover, TsEV-treated DCs possessed a high capacity to induce conventional FoxP3 + regulatory T cells, as well as unconventional T regulatory (Tr1) cells. Tolerogenic properties of TsEV-treated DCs were retained even after challenge with a pro-inflammatory stimulus. These findings highlight the potential of TsEVs to induce immune tolerance, suggesting their potential use as therapeutics for the treatment of inflammatory disorders.

2025-04-01·Molecular Therapy

Development of RelB-targeting small-molecule inhibitors of non-canonical NF-κB signaling with antitumor efficacy

Article

作者: Yang, Zhuo ; Tao, Yu ; Shi, Yufang ; Li, Lingling ; Wang, Qi ; Liu, Zhanjie ; Xie, Ningxia ; Jiang, Yuhang ; Liu, Yongzhong ; Li, Bo ; Chen, Xi ; Zhu, Weiliang ; Xu, Zhijian ; Liu, Dandan ; Sun, Donglin ; Zhang, Haohao ; Lin, Han ; Ye, Deji ; Hu, Yiming ; Zhang, Jie ; Wei, Shuqi ; Liu, Sanhong ; Zhang, Xiaoren ; Li, Cuifeng

Dysfunction of the non-canonical nuclear factor κB (NF-κB) signaling pathway has been causally associated with numbers of cancers and autoimmune diseases. However, specific inhibitors for this signaling pathway remain to be developed. Here, we showed that structure-based cell-based screening yielded a potent and specific small molecule targeting RelB to inhibit the non-canonical NF-κB signaling pathway, while it had no inhibitory effect on the canonical NF-κB signaling pathway. Mechanistically, the inhibitor directly interacted with RelB protein and disrupted RelB binding to its target DNA, thus repressing RelB transactivity on target genes. Through blocking oncogenic activity of the non-canonical NF-κB signaling pathway in colorectal cancer or B lymphoma, the inhibitor efficiently exerted a potent antitumor effect in vitro and in vivo. Thus, our study provided a new RelB-targeting inhibitor that inhibited the non-canonical NF-κB signaling pathway and facilitated precise therapeutic applications in cancers and possibly other diseases.

项与 RELB 相关的新闻（医药）

2023-12-28

·今日头条

新型抑制剂！联合治疗可克服耐药！厦门大学发现结肠癌治疗新策略

本文为转化医学网原创，转载请注明出处作者：Jerry 导读：结直肠癌(CRC)对免疫治疗的耐药性与FAS (Apo-1或CD95)依赖性细胞凋亡的阻碍有关，FAS是癌症的一个标志。 2023年12月26日，厦门大学研究人员在期刊《Advanced Science》上发表了题为“Pirin Inhibits FAS-Mediated Apoptosis to Support Colorectal Cancer Survival”的研究论文，研究表明，结肠癌中pirin (PIR)蛋白的上调促进了肿瘤的发生。敲除或抑制PIR可显著增加小鼠的FAS表达、FAS依赖性细胞凋亡并减轻结直肠肿瘤的形成。结果表明PIR-NIK-NFκB2-FAS存活通路在支持结直肠癌存活中起关键作用。 https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202301476 研究背景 01 PIR (Pirin)是cupin超家族蛋白的一员，最初在酵母双杂交筛选中被鉴定为核因子I/CCAAT盒转录因子(NFI/CTF1)的相互作用因子。它在人体几乎所有组织中普遍表达，主要分布在细胞核和细胞质中。近年来，越来越多的证据表明PIR与几种癌症有关，包括结肠癌、乳腺癌和黑色素瘤，它可能是癌症生长和恶性肿瘤的刺激物。此外，PIR已被确定为NRF2的靶标，并在人类结直肠癌中过表达，功能未知。结直肠癌是一种起源于结肠或直肠的恶性肿瘤。在本研究中，研究人员旨在确定PIR在CRC中促进肿瘤发生的确切生物学功能和相应的机制。为了解决这些问题，研究人员在HCT116细胞中敲除(KD) PIR，观察到严重的细胞凋亡和显著的FAS上调，表明PIR可能是FAS表达的抑制因子。 NFκB家族由转录因子RELA (p65)、RELB、c-REL、NFκB1 (p105/p50)和NFκB2 (p100/p52)组成，属于典型和非典型NFκB通路。典型的nf - κ b1通路的激活依赖于i - κ b α的蛋白酶体降解，导致由p50和p65/c-REL组成的蛋白复合物的激活。相反，非规范或替代nf - κ b2途径的激活在很大程度上依赖于p100前体的选择性蛋白酶体降解，以产生与RELB形成异源二聚体的蛋白片段p52。然后，p52/RELB复合体作为功能性转录因子。nf - κ b诱导激酶(NIK)在p100的加工和激活中起关键作用。据报道，尽管NFκB2的主要功能是调节免疫应答，但在某些死亡诱导信号刺激下，它作为促凋亡蛋白发挥作用。研究进展 02 本研究中，研究人员报告了PIR蛋白在保护癌细胞免受CD8+杀手T细胞凋亡中的作用，其机制包括破坏FAS转录活性和阻断FAS膜易位。我们研究的重点是内源性FAS蛋白的表达及其在细胞膜上的易位在CD8+ T淋巴细胞介导的细胞凋亡中的重要性。在FAS表达调控方面，研究人员发现成熟的nf - κ b2复合物(p52-RELB)而非nf - κ b1复合物(p50-RELA)在结直肠癌中通过直接结合其启动子区域并激活其转录来调控FAS表达。研究人员进一步发现PIR是NFκB2介导的FAS转录活性的强抑制因子。PIR通过两种方式抑制NFκB2。通过这些方式，PIR显著抑制FAS表达。此外，PIR与FAS相互作用并将其保留在细胞质中，阻止其膜易位。综上所述，研究人员建立了PIR-NIK-NFκB2-FAS生存信号转导通路，提示PIR是一个重要的生存因子，通过多种机制抑制基于FAS的细胞凋亡，促进结直肠癌恶性发展。在这项研究中，研究人员也提供了令人信服的证据，证明PIR可能是一个新的治疗结直肠癌的靶点。首先，即使没有上游启动子如FAS配体或FAS单抗的刺激，PIR KD或PIR抑制剂引起的内源性FAS上调也能显著触发细胞凋亡。这一观察在结肠特异性PIR敲除小鼠中得到了证实，这些小鼠表现出高水平的FAS表达，并显著延缓了AOM/ dss诱导的结肠癌形成。其次，野生型HCT116细胞或高表达PIR的HT29细胞对FAS mAb或CD8+ T细胞诱导的细胞死亡具有抗性，相反，适度下调PIR即使不足以启动细胞凋亡，也可以显著增强HCT116结直肠癌细胞对FAS mAb或CD8+ T细胞诱导的细胞死亡的敏感性。第三，PIR抑制剂可显著抑制HCT116细胞移植瘤的生长。综上所述，抑制PIR可能是治疗高水平PIR和低水平FAS的CRC的一种有前景的策略。抑制PIR可减轻结肠癌的形成研究结论 03 根据研究人员的发现，PIR抑制剂可以通过刺激肿瘤内源性FAS表达及其膜易位来增强CD8+杀伤T细胞的抗肿瘤活性，PIR抑制剂与免疫检查点阻断联合可能是治疗结直肠癌的潜在策略，特别是那些免疫治疗耐药的结直肠癌。因此，未来迫切需要开发更有效的PIR抑制剂。参考资料： https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202301476 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 北京｜12月19日-20日 ▶第四届单细胞测序技术应用研讨会暨单细胞&空间组学研讨会（日程稍后公布）点击对应文字查看详情

免疫疗法

2022-12-19

·药研网

癌症及自免疫靶点：OX40

01靶点介绍OX40是肿瘤坏死因子受体（TNFR）家族的成员，也称为CD134或TNFRSF44。OX4于1987年首次在活化的大鼠CD4+T细胞表面发现。随后研究表明，OX40在活化的CD4+和CD8 +T细胞、中性粒细胞和自然杀伤（NK）细胞上均有表达。OX40是一种Ⅰ型跨膜糖蛋白，由约275个氨基酸组成，具有三个全半胱氨酸结构域（CRD）和一个部分C端CRD，分子量约为50kDa。OX40结构[1]OX40是由配体激活的T细胞共刺激物，在自身免疫、传染病和癌症的多种动物模型中介导CD4+和CD8+T细胞的存活和扩增，还参与控制效应T细胞和记忆T细胞反应。OX40的配体（OX40L,也称为CD252）是TNFR受体超家族 (TNFRSF) 的成员。OX40L是一种II型糖蛋白，具有包括23个氨基酸的胞浆尾部和包括133个氨基酸的细胞外结构域。 hOX40-OX40L 相互作用[1]OX40L主要表达于活化的抗原呈递细胞（APC），如树突状细胞（DC）、活化的B细胞和巨噬细胞。此外，还表达于造血细胞，如活化的NK细胞、肥大细胞或应答的CD4+T细胞，以及非造血细胞，例如内皮细胞或平滑肌细胞。02信号通路OX40L是三聚体，每个OX40L与三个OX40分子结合。OX40信号复合物通过多种途径调控转录：TRAF2/5/6、IKKα、IKKβ、IKKγ、IκB被磷酸化和降解，然后RelA和p50进入细胞核；在依赖TRAF6的过程中，IKKα作用于RelB，使其入核进入；OX40信号复合物磷酸化STAT5，使STAT5入核；OX40允许钙进入细胞内，然后通过钙调素激活钙调磷酸酶，导致NFAT脱磷酸化并进入细胞核内；激活的OX40信号复合物通过PI3K及PDK增加AKT磷酸化，进而使得IKK复合物信号传导增强。NFAT和PI3K通路可以放大来自抗原刺激的T细胞受体的信号，包括FoxP3转录的抑制和BLIMP-1的转录增加。OX40刺激后的信号通路[2]03疾病治疗OX40及其同源配体OX40L在免疫调节中的作用，尤其是作为治疗靶点，越来越受到关注。它在自免疫和癌症治疗领域均具有重要作用。自免疫和炎症性疾病在自身免疫中，OX40通常在炎症部位上调，如血管炎、类风湿性关节炎、结肠炎和实验性自身免疫性脑脊髓炎(EAE)等。通过阻断OX40：OX40L的相互作用，可以改善疾病症状。癌症治疗OX40信号可以促进非调节性CD4+和CD8 +T细胞存活，维持抗凋亡蛋白表达（BCL-XL、BCL-2和BFL1），增强IL-2、IL-4、IL-5和IFN-g的细胞因子产生，增强肿瘤特异性T细胞免疫应答，并在抗原攻击后增加肿瘤特异性记忆T细胞生成。癌症免疫治疗中靶向OX40-OX40L相互作用的原理示意图[3]目前的抗H_OX40的mAbs主要用于以下三种情况：使用激动剂mAb直接刺激效应T细胞（CD4+和CD8+），增加细胞的增殖和存活功能；激动剂mAb作用于Tregs，可减弱Tregs的抑制功能；用缺失的mAb消除Tregs，导致效应细胞的抑制功能降低。上述三种方法的组合使用也是可行的。抗H_OX40mAbs作为癌症免疫疗法的潜在作用模式[1]04竞争格局目前国内国外多家药企对OX40展开布局，国外如辉瑞、阿斯利康、安进、赛诺菲、BMS等，国内如君实、百济神州和信达生物等。吉满生物提供OX40表达细胞系 → https://www.ddxcell.cn/search.php?pros=OX40扫码查询现货细胞系参考：1. DOI:10.1016/j.molimm.2017.01.006 2. DOI: 10.1007/s12016-015-8498-3. 3. DOI: 10.1016/j.apsb.2019.08.010. 往期推荐重磅！Moderna/默沙东癌症疫苗IIb期达主要终点PROTAC全球布局一览最新：42家已获批新冠病毒抗原检测试剂盒点击下方“药研网”，关注更多精彩内容

免疫疗法

2022-08-18

·生物谷

Int J Mol Sci：消炎药倍他米松有望用于减少前列腺癌放疗的副作用

在一项新的研究中，来自美国肯德基大学和威斯康星大学麦迪逊分校的研究人员发现作为一种常见的类固醇，消炎药倍他米松（betamethasone）可能能够用于减少前列腺癌放疗的副作用。在一项新的研究中，来自美国肯德基大学和威斯康星大学麦迪逊分校的研究人员发现作为一种常见的类固醇，消炎药倍他米松（betamethasone）可能能够用于减少前列腺癌放疗的副作用。相关研究结果近期发表在International Journal of Molecular Sciences期刊上，论文标题为“The RelB-BLNK Axis Determines Cellular Response to a Novel Redox-Active Agent Betamethasone during Radiation Therapy in Prostate Cancer”。论文通讯作者、肯德基大学医学院毒理学与癌症生物学系助理教授Luksana Chaiswing博士及其研究团队首次证实，倍他米松能保护正常的前列腺细胞免受放疗的伤害，同时使癌细胞对这种治疗更敏感。前列腺癌是美国男性癌症死亡的第二大原因。虽然放疗对控制前列腺癌的生长很重要，但它有增加副作用的巨大风险，包括对正常组织的伤害。 Chaiswing说，“迫切需要旨在保护正常组织不受伤害同时又能提高放疗效果的新疗法。这种方法的开发将对前列腺癌的控制和患者的生活质量产生重大影响。” 这些作者筛选了大约700种获得美国食品药品管理局（FDA）批准的药物的特性，包括保护非癌细胞免受放疗诱导的细胞毒性、对前列腺癌细胞的杀伤性、增加癌细胞和非癌细胞中的过氧化氢水平。 FDA批准的药物文库筛选，以便找出诱导前列腺癌细胞死亡同时通过介导过氧化氢产生增加非癌前列腺细胞活力的化合物。图片来自International Journal of Molecular Sciences, 2022, doi:10.3390/ijms23126409。作为一种被批准用于治疗炎症和造血系统癌症的皮质类固醇，倍他米松是具有所有理想特性的前五种药物之一。倍他米松增加过氧化氢水平，从而激活正常的、非癌前列腺细胞中一种名为“RelB”的保护性蛋白。 Chaiswing说，“这项研究的结果可能导致一种新的抗癌方案，该方案通过使肿瘤组织对放疗敏感同时保护正常组织不受放疗引起的副作用影响，从而提高放疗的疗效，这可能导致癌症幸存者的生活质量的改善。”（生物谷 Bioon.com）参考资料： Luksana Chaiswing et al. The RelB-BLNK Axis Determines Cellular Response to a Novel Redox-Active Agent Betamethasone during Radiation Therapy in Prostate Cancer. International Journal of Molecular Sciences, 2022, doi:10.3390/ijms23126409.