更新于：2024-05-01

IFNAR-1

干扰素α/β受体α链

更新于：2024-05-01

基本信息

别名

CRF2-1、Cytokine receptor class-II member 1、Cytokine receptor family 2 member 1

+ [9]

简介

Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:2153461, PubMed:7813427, PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:24075985, PubMed:21854986, PubMed:31270247, PubMed:33252644, PubMed:35442418). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:7665574, PubMed:10049744, PubMed:21854986). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:7813427, PubMed:7665574, PubMed:21854986, PubMed:32972995). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (PubMed:7813427, PubMed:7526154, PubMed:7665574, PubMed:21854986, PubMed:32972995). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:7813427, PubMed:7665574, PubMed:9121453, PubMed:19561067, PubMed:21854986, PubMed:32972995). Can also act independently of IFNAR2: form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity).

关联

项与 IFNAR-1 相关的药物

Anifrolumab-FNIA

靶点

IFNAR-1

作用机制

IFNAR-1拮抗剂

在研机构

MedImmune Pharma BV [+6]

原研机构

MedImmune LLC

在研适应症

系统性红斑狼疮 [+7]

非在研适应症

类风湿关节炎

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2021-07-30

Recombinant human interferon alpha-1b(Beijing Tri-Prime Gene Pharmaceutical Co Ltd)

重组人干扰素α1b(北京三元基因药业股份有限公司)

靶点

IFNAR-1

作用机制

IFNAR-1刺激剂

在研机构

原研机构

在研适应症

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1999-01-01

Recombinant human interferon alpha-1b(Changchun Institute of Biological Products)

重组人干扰素α1b滴眼液 (长春生物制品研究所)

靶点

IFNAR-1

作用机制

IFNAR-1刺激剂

在研机构

长春生物制品研究所有限责任公司

原研机构

长春生物制品研究所有限责任公司

在研适应症

眼部感染

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1996-01-01

102

项与 IFNAR-1 相关的临床试验

NCT06374212 / Not yet recruiting临床2期IIT

A Prospective Open-label Trial Examining the Efficacy and Safety of Anifrolumab for Hidradenitis Suppurativa (HS)

This clinical trial aims to study if a drug called anifrolumab works to treat Hidradenitis Suppurativa (HS) as well as its effect in quality of life before and after treatment. Anifrolumab is a monoclonal antibody that inhibits several processes that have been shown to be involved in the development of HS.
The study lasts approximately 40 weeks separated into a screening, treatment, and follow-up phase. Researchers determine if it is safe for the you to receive the drug and if you are eligible for the study during Screening. If eligible for the study, the treatment phase lasts 24 weeks (or six months) with one follow-up visit 12 weeks after the last visit in the treatment phase.
During the treatment phase, participants will be asked to come to clinic every two weeks for the first month of treatment, and monthly thereafter for a total of eight treatment visits. Participants will be asked to:
Complete questionnaires asking about the effect of HS in their daily lives and their perception of HS and treatment received.
Receive related medical evaluation
Receive the study drug intravenously
Stay 20 minutes after the infusion for monitoring

开始日期2024-06-01

申办/合作机构

The University of North Carolina at Chapel Hill

[+1]

NCT06015737 / Not yet recruiting临床3期

A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase III Study to Evaluate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/or Subacute Cutaneous Lupus Erythematosus Who Are Refractory and/or Intolerant to Antimalarial Therapy

This study aims to evaluate the efficacy and safety of subcutaneous (SC) anifrolumab versus placebo in adult participants with cutaneous lupus erythematosus (CLE).

开始日期2024-05-09

申办/合作机构

AstraZeneca PLC

[+1]

NCT06363370 / Recruiting临床3期

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Safety and Efficacy of Human Interferon α1b Inhaled Solution in the Treatment of Respiratory Syncytial Virus Lower Respiratory Tract Infection in Children.

To evaluate the efficacy and safety of interferon α1b (GB05) in the treatment of children under 2 years of age with respiratory syncytial virus infection.

开始日期2024-03-27

申办/合作机构

科兴生物制药股份有限公司

100 项与 IFNAR-1 相关的临床结果

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100 项与 IFNAR-1 相关的转化医学

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0 项与 IFNAR-1 相关的专利（医药）

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4,305

项与 IFNAR-1 相关的文献（医药）

2024-03-01·Hepatology communications

Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis.

Article

作者: Rebekka J S Salzmann ; Christina Krötz ; Tudor Mocan ; Lavinia P Mocan ; Cristiana Grapa ; Sophia Rottmann ; Ramona Reichelt ; Cindy M Keller ; Bettina Langhans ; Frederik Schünemann ; Alexander Pohl ; Thomas Böhler ; Käthe Bersiner ; Marcin Krawczyk ; Piotr Milkiewicz ; Zeno Sparchez ; Frank Lammert ; Sebastian Gehlert ; Maria A Gonzalez-Carmona ; Arnulf Willms ; Christian P Strassburg ; Miroslaw T Kornek ; Leona Dold ; Veronika Lukacs-Kornek

BACKGROUND:

The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression.

METHODS:

Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients' sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study.

RESULTS:

Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2-deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, β and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC.

CONCLUSIONS:

The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.

2024-02-22·NPJ vaccines

No link between type I interferon autoantibody positivity and adverse reactions to COVID-19 vaccines.

Article

作者: Ahmet Yalcinkaya ; Marco Cavalli ; Axel Cederholm ; Maribel Aranda-Guillén ; Anish Behere ; Hedvig Mildner ; Tadepally Lakshmikanth ; Laura Gonzalez ; Constantin Habimana Mugabo ; Anette Johnsson ; Olov Ekwall ; Olle Kämpe ; Sophie Bensing ; Petter Brodin ; Pär Hallberg ; Mia Wadelius ; Nils Landegren

Type I interferons act as gatekeepers against viral infection, and autoantibodies that neutralize these signaling molecules have been associated with COVID-19 severity and adverse reactions to the live-attenuated yellow fever vaccine. On this background, we sought to examine whether autoantibodies against type I interferons were associated with adverse events following COVID-19 vaccination. Our nationwide analysis suggests that type I interferon autoantibodies were not associated with adverse events after mRNA or viral-vector COVID-19 vaccines.

2024-02-20·American journal of physiology. Lung cellular and molecular physiology

Anti-Inflammatory Roles of Type I Interferon Signaling in the Lung.

Article

作者: Jingjing Feng ; Yi Liu ; Jooyoung Kim ; Farida Ahangari ; Naftali Kaminski ; William G Bain ; Zhijun Jie ; Charles S Dela Cruz ; Lokesh Sharma

Excessive or persistent inflammation may have detrimental effects on lung structure and function. Currently, our understanding of conserved host mechanisms that control the inflammatory response remains incompletely understood. In this study, we investigated the role of type I interferon signaling in the inflammatory response against diverse clinically relevant stimuli. Using mice deficient in type I interferon signaling (IFNAR1-/-), we demonstrate that the absence of interferon signaling resulted in a robust and persistent inflammatory response against Pseudomonas aeruginosa, lipopolysaccharide, and chemotherapeutic agent bleomycin. The elevated inflammatory response in IFNAR1-/- mice was manifested as elevated myeloid cells such as macrophages and neutrophils, in the broncho-alveolar lavage. The inflammatory cell response in the IFNAR1-/- mice persisted to 14 days and there is impaired recovery and fibrotic remodeling of the lung in IFNAR1-/- mice after bleomycin injury. In the Pseudomonas infection model, the elevated inflammatory cell response led to improved bacterial clearance in IFNAR1-/- mice, although there was similar lung injury and survival. We performed RNA-sequencing of lung tissue in wildtype and IFNAR1-/- mice after LPS and bleomycin injury. Our unbiased analysis identified differentially expressed genes between IFNAR1-/- and wild-type mice, including previously unknown regulation of NOD-like receptor signaling, RIG-I signaling, and necroptosis pathway by type I interferon signaling in both models. These data provide novel insights into the conserved anti-inflammatory mechanisms of the type I interferon signaling.

项与 IFNAR-1 相关的新闻（医药）

2024-03-20

·药渡

荃信生物昨日港股上市：开盘大涨40%

临床3期IPO生物类似药临床1期

2024-03-20

·药研网

荃信生物今日正式在港交所上市，大涨33%！

3月20日，据荃信生物近日在港交所发布的公告，该公司将于今日在港交所正式上市。公告显示，公司全球发售1204.64万股股份，最终发售价每股19.8港元，全球发售净筹约1.63亿港元，每手200股。荃信生物-B(02509)新股发行后，截至发稿，走势直接大涨33%！创新药企的价值在于企业的差异化创新研发能力和产品的商业化潜力两大关键要素。对于投资者和市场而言，药企的研发实力和管线情况是评估其潜在市值和长期价值的重要参考。荃信生物研发实力如何？荃信生物创办于2015年，专注于开发治疗自身免疫性疾病及过敏性疾病的生物疗法，是目前国内在自身免疫性疾病及过敏性疾病方面获最多临床试验申请（IND）批准的药企之一。从研发和管线来看，荃信生物近年来不断加大研发投入。招股书显示，荃信生物的研发开支由2021年的1.52亿元增至2022年的2.57亿元，同比增长69.35%，并于2023年增3.644亿元，连年增长的研发开支足以体现出其对研发的重视程度。图源招股书体现到产品上，荃信生物有两个核心产品——IL-17A抑制剂QX002N、抗IL-4Rα单抗QX005N，它们目前分别处于3期和2期临床研究阶段。此外，管线还有其它七种候选药物处于不同的研究阶段。产品管线涉及靶点包括IL-17A、IL-33、TSLP、IFNAR1等，涵盖了自身免疫和过敏性疾病的四个主要领域，即皮肤、风湿、呼吸道及消化道疾病；适应症包括银屑病、特应性皮炎、系统性红斑狼疮、中重度哮喘等。荃信生物在研管线两款核心产品QX002N（IL-17A单抗）QX002N是一种人源化IgG1单克隆抗体，旨在用于特异性结合IL-17A，包括IL-17AA和IL-17AF，从而阻断其与预期受体复合物的结合，包括白细胞介素17受体A（IL-17RA）及白细胞介素17受体C（IL-17RC），并阻止若干促炎信号通路的后续激活。QX002N的作用机制|图源：招股书在II期临床试验中，每4周一次接受QX002N（160mg）的受试者在第16周时的ASAS20及ASAS40应答率分别达到60.0%及40.0%。目前QX002N治疗强直性脊柱炎（AS）的III期临床试验已启动，预计在2025年下半年完成。QX005N（IL-4Rα单抗）QX005N是一种阻断IL-4Rα的单克隆抗体。IL-4Rα是一种经过临床验证的靶点，由于IL-4Rα控制IL-4及IL-13的信号传导，这对于2型炎症的发生至关重要。目前，QX005N已获得7项IND批准，分别用于治疗成人特应性皮炎（AD）、青少年AD、结节性痒疹、慢性鼻窦炎伴鼻息肉（CRSwNP）、慢性自发性荨麻疹、哮喘及慢性阻塞性肺病，已在中国启动用于AD、结节性痒疹及CRSwNP的2期临床试验。QX005N的作用机制|图源：招股书QX005N已经在1a期及1b期临床试验中显示出对治疗特应性皮炎具良好的安全性及疗效。在中重度特应性皮炎患者的1b期临床试验中，300mg和600mg组于第12周中有75.0%的受试者达到湿疹面积及严重程度指数-75（EASI-75）反应，而50.0%的受试者达到研究者整体评估（IGA）分数（0或1），且没有明显增加安全风险。目前荃信生物已在中国启动QX005N用于特应性皮炎、结节性痒疹及慢性鼻窦炎合并鼻息肉的II期临床试验。2024年1月，CDE授予公司核心产品QX005N治疗结节性痒疹（PN）的突破性疗法资格认定。一方面意味着该产品相较现有疗法有着更优的临床效益以及创新性，另一方面也意味着其能够获得CDE快速审评待遇，加快研发进程。产品商业化潜力如何其次来分析产品的商业化潜力。荃信生物聚焦的自免和过敏性疾病市场是全球第二大疾病治疗的领域。据美国自身免疫相关疾病协会（AARDA）统计，近几年各类自免疾病患者群体约占全球总人口比例的7.6%-9.4%。弗若斯特沙利文的统计数据则显示，全球各类自免疾病患者规模近5亿人，2022年全球自免药物市场规模约达1323亿美元，已成为继肿瘤之后的第二大疾病市场。弗若斯特沙利文预测，到2030年，全球自免药物市场规模有望达到1760亿美元，2022~2030年复合年增长率为3.6%，其中中国自免药物市场规模2030年有望达到近250亿美元，较2020年实现十倍增长，是全球自免药物的重要增量来源。1QX005NQX005N是一种阻断IL-4Rα的单克隆抗体，目前处于II期临床试验阶段。据悉，全球首个获FDA批准上市的IL-4Rα抑制剂度普利尤单抗，于2023年取得117亿美元的年销售额，是全球最畅销的过敏性疾病生物药物之一，其2023年中国市场销售额也达到了约30亿元人民币（预计）。2QX001S又以荃信生物预期于2024年底商业化的QX001S为例，作为第一个在中国提交BLA的国产乌司奴单抗生物类似药用于治疗银屑病，其也有可能成为中国首个获批的乌司奴单抗生物类似药。弗若斯特沙利文预计，2030年中国银屑病患者有680万人，其中20%至30%患有中重度疾病，药物市场规模将达到99亿美元（约超700亿元人民币），QX001S后续的商业化销售空间可期。3QX013N再譬如针对治疗慢性自发性荨麻疹（CSU）的QX013N。根据诺华的流病调研数据，慢性荨麻疹最大的患者人群在中国：中国有510万患者接受治疗，200万未受控制（使用抗组胺药后），且有10万患者在使用生物制剂；而美国、欧洲5国和日本等地区接受治疗的患者数量总和为330万，未受控制患者数量为150万，均逊于中国，显示出CSU在中国的巨大治疗需求。度普利尤单抗的成功销售额为QX005N提供了有力的市场参考，若日后QX005N顺利上市，其或也有望展现出可观的销售前景。小结总的来说，持续的研发投入、核心产品的突破性疗法资格认定、领先的临床进展、探索未被成熟开发的潜力靶点、未被满足的患者需求等种种成果，都充分展现出荃信生物强劲的差异化创新研发能力和产品管线庞大的商业化潜力，能够持续为投资人创造价值。这一演绎路径或将推动公司的价值曲线不断攀升，值得关注。荃信生物，未来可期。细胞系产品查询投稿丨商务合作转载丨加交流群往期推荐一国产GLP-1药企递交IPO招股书，估值约8.3亿元人民币超40亿美元：上海Argo与Novartis达成多项目RNAi独家合作17 亿美元！强生与LegoChem就Trop2 靶向ADC的达成许可协议完整版：2023 全年药企裁员汇总点击下方“药研网”，关注更多精彩内容

临床3期临床2期临床申请申请上市IPO

2024-03-20

·医药笔记

荃信生物今日港股上市：开盘大涨40%

▎Armstrong2024年3月20日，荃信生物登陆港股上市，发行价19.8港元，开盘大涨40%至27.4港元。荃信生物此次IPO基石投资者有3家，华东医药、Beevest capital各认购500万美元，健鑫医药认购1500万美元，合计2500万美元。荃信生物成立于2015年，拥有特色的兔抗体技术平台，研发管线聚焦自身免疫病，生物类似药乌司奴单抗已经申报上市，预计今年四季度获批。创新药方面，IL-17A抗体处于三期临床，IL-4R抗体、IL-23p19抗体处于二期临床，IFNAR1抗体、TSLP抗体处于一期临床。信生物研发管线覆盖皮肤疾病、风湿、呼吸系统疾病、消化系统疾病等多个治疗领域。荃信生物成立于2015年，成立以来完成轮融资，2022年3月完成2.275亿元人民币C轮融资，投前估值33亿元，投后估值35.275亿元。总结荃信生物此次IPO之前的股权架构如下，华东医药持股17.09%，洪泰健康持股8.93%，经纬创投持股4.69%等。Armstrong技术全梳理系列GPRC5D靶点全梳理；CD40靶点全梳理；CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向；Claudin 6靶点全梳理；Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇；CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理；Ambrx技术全梳理；Vir Biotech技术全梳理；Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；科望医药技术全梳理2.0；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理；Momenta技术全梳理；NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

IPO临床3期抗体药物偶联物临床2期生物类似药