Imaprelimab(Imaprelimab) - 药物靶点：Muc18_在研适应症：多发性硬化症_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-CD146-monoclonal-antibody、Anti-MCAM-monoclonal-antibody

靶点

Muc18

作用机制

Muc18抑制剂(黑色素瘤细胞粘附分子抑制剂)

治疗领域

免疫系统疾病神经系统疾病其他疾病

在研适应症

多发性硬化症

非在研适应症

炎症肿瘤银屑病

原研机构

Neotope Biosciences Ltd.

在研机构

Wenbli Therapeutics, Inc.

非在研机构

Prothena Biosciences Ltd.Prothena Corp. Plc

最高研发阶段药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 9946679H

来源: *****

Sequence Code 9946653L

来源: *****

关联

2

项与 Imaprelimab 相关的临床试验

NCT02630901 / Completed临床1期

A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study of PRX003 Administered by Intravenous Infusion in Subjects With Psoriasis

This multiple ascending dose study is to determine safety, tolerability, pharmacokinetics and immunogenicity of PRX003 in approximately 56 patients with Psoriasis.

开始日期2016-03-17

申办/合作机构

Prothena Biosciences Ltd.

NCT02458677 / Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of PRX003 Administered by Intravenous Infusion in Healthy Subjects

This single ascending dose study is to determine safety, tolerability, pharmacokinetics and immunogenicity of PRX003 in approximately 40 healthy subjects.

开始日期2015-05-01

申办/合作机构

Prothena Biosciences Ltd.

100 项与 Imaprelimab 相关的临床结果

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100 项与 Imaprelimab 相关的转化医学

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100 项与 Imaprelimab 相关的专利（医药）

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6

项与 Imaprelimab 相关的文献（医药）

2023-06-28·Cell journal

Peroxiredoxin 3 Inhibits Cardiac Fibrosis in Mice via NOX4-P38 Signalling.

Article

作者: Li, Jun ; Xiong, Xiaoqi ; Kang, Yi ; Zhang, Jing ; Luo, Changjun ; Li, Bing ; Nong, Xiuhong ; Wei, Wei ; Ai, Fen ; Chen, Zhen

OBJECTIVEPeroxiredoxin-3 (Prx-3) is widely acknowledged as an antioxidant that protects against mitochondrial reactive oxygen species. Nonetheless, its role in cardiac fibrosis has not been elucidated. We aim to explore the role and mechanism of Prx-3 in cardiac fibrosis.MATERIALS AND METHODSIn this experimental study, mice received subcutaneous injections of isoproterenol (ISO) for 14 consecutive days (10 mg/kg/d for three days, followed by 5 mg/kg/d for 11 days) to establish a cardiac fibrosis model. The mice were subsequently injected with adenovirus-Prx-3 (ad-Prx-3) to enable Prx-3 overexpression. Echocardiography was used to evaluate cardiac function. Mice heart fibroblasts were isolated and stimulated with transforming growth factor β1 (TGFβ1) to induce fibrosis in vitro. Cells were also transfected with ad-Prx-3 for overexpression of Prx-3.RESULTSEchocardiographic diameters and fibrosis markers indicated that Prx-3 could inhibit ISO-induced cardiac dysfunction and fibrosis. Fibroblasts with Prx-3 overexpression exhibited reduced activation, proliferation, and collagen transcription. We found that Prx-3 reduced the expression of NADPH oxidase 4 (NOX4) and reduced P38 levels. After treatment with a P38 inhibitor, the Prx-3 overexpression-induced anti-fibrosis effect was mitigated.CONCLUSIONPrx-3 could protect against ISO-induced cardiac fibrosis by inhibiting the NOX4-P38 pathway.

2019-05-01·Molecular Cancer Research

Therapeutic Targeting of CD146/MCAM Reduces Bone Metastasis in Prostate Cancer

Article

作者: Kruithof-de Julio, Marianna ; Chen, Lanpeng ; Ng, Charlotte K.Y. ; van der Pluijm, Gabri ; Grosjean, Joël ; Cecchini, Marco G. ; Thalmann, George N. ; Zoni, Eugenio ; Kloen, Peter ; Melsen, Janine ; Piscuoglio, Salvatore ; Astrologo, Letizia ; Klima, Irena ; Snaar-Jagalska, Ewa B. ; Flanagan, Kenneth

AbstractProstate Cancer is the most common cancer and the second leading cause of cancer-related death in males. When prostate cancer acquires castration resistance, incurable metastases, primarily in the bone, occur. The aim of this study is to test the applicability of targeting melanoma cell adhesion molecule (MCAM; CD146) with a mAb for the treatment of lytic prostate cancer bone metastasis. We evaluated the effect of targeting MCAM using in vivo preclinical bone metastasis models and an in vitro bone niche coculture system. We utilized FACS, cell proliferation assays, and gene expression profiling to study the phenotype and function of MCAM knockdown in vitro and in vivo. To demonstrate the impact of MCAM targeting and therapeutic applicability, we employed an anti-MCAM mAb in vivo. MCAM is elevated in prostate cancer metastases resistant to androgen ablation. Treatment with DHT showed MCAM upregulation upon castration. We investigated the function of MCAM in a direct coculture model of human prostate cancer cells with human osteoblasts and found that there is a reduced influence of human osteoblasts on human prostate cancer cells in which MCAM has been knocked down. Furthermore, we observed a strongly reduced formation of osteolytic lesions upon bone inoculation of MCAM-depleted human prostate cancer cells in animal model of prostate cancer bone metastasis. This phenotype is supported by RNA sequencing (RNA-seq) analysis. Importantly, in vivo administration of an anti-MCAM human mAb reduced the tumor growth and lytic lesions. These results highlight the functional role for MCAM in the development of lytic bone metastasis and suggest that MCAM is a potential therapeutic target in prostate cancer bone metastasis.Implications:This study highlights the functional application of an anti-MCAM mAb to target prostate cancer bone metastasis.

2009-07-01·Biochemical Journal3区 · 生物学

Mitochondrial peroxiredoxin 3 is more resilient to hyperoxidation than cytoplasmic peroxiredoxins

3区 · 生物学

Article

作者: Pearson, Andree G. ; Lowther, W. Todd ; Hampton, Mark B. ; Winterbourn, Christine C. ; Jönsson, Thomas J. ; Pullar, Juliet M. ; Cox, Andrew G.

The Prxs (peroxiredoxins) are a family of cysteine-dependent peroxidases that decompose hydrogen peroxide. Prxs become hyperoxidized when a sulfenic acid formed during the catalytic cycle reacts with hydrogen peroxide. In the present study, Western blot methodology was developed to quantify hyperoxidation of individual 2-Cys Prxs in cells. It revealed that Prx 1 and 2 were hyperoxidized at lower doses of hydrogen peroxide than would be predicted from in vitro data, suggesting intracellular factors that promote hyperoxidation. In contrast, mitochondrial Prx 3 was considerably more resistant to hyperoxidation. The concentration of Prx 3 was estimated at 125 μM in the mitochondrial matrix of Jurkat T-lymphoma cells. Although the local cellular environment could influence susceptibility, purified Prx 3 was also more resistant to hyperoxidation, suggesting that despite having C-terminal motifs similar to sensitive eukaryote Prxs, other structural features must contribute to the innate resilience of Prx 3 to hyperoxidation.

100 项与 Imaprelimab 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
银屑病	临床2期	美国	Prothena Biosciences Ltd.	2015-05-01
炎症	临床2期	爱尔兰	Prothena Corp. Plc	-
肿瘤	临床2期	爱尔兰	Prothena Corp. Plc	-
多发性硬化症	药物发现	爱尔兰	Wenbli Therapeutics, Inc.	-