更新于：2024-04-01

CCR2

C-C趋化因子受体2型

更新于：2024-04-01

基本信息

别名

CCR2受体、C-C chemokine receptor type 2、C-C CKR-2

+ [11]

简介

Key functional receptor for CCL2 but can also bind CCL7 and CCL12 (PubMed:8146186, PubMed:8048929, PubMed:23408426). Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B (PubMed:23938203). Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation (By similarity). Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (By similarity). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity). Mediates the recruitment of macrophages and monocytes to the injury site following brain injury (By similarity). (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.

关联

项与 CCR2 相关的药物

Cenicriviroc mesylate

靶点

CCR2 x CCR5

作用机制

CCR2拮抗剂 [+1]

在研机构

Tobira Therapeutics, Inc. [+2]

原研机构

Tobira Therapeutics, Inc.

在研适应症

肥胖 [+4]

非在研适应症

获得性免疫缺陷综合征 [+14]

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

Plozalizumab

靶点

CCR2

作用机制

CCR2拮抗剂

在研机构

Millennium Pharmaceuticals, Inc.

原研机构

Millennium Pharmaceuticals, Inc.

在研适应症

糖尿病肾病

非在研适应症

动脉粥样硬化 [+8]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Gemcabene Calcium

吉卡宾

靶点

CCR2 x CCR5 x PPAR

作用机制

CCR2拮抗剂 [+2]

在研机构

Gemphire Therapeutics, Inc.

原研机构

Gemphire Therapeutics, Inc.

在研适应症

高血压 [+2]

非在研适应症

新型冠状病毒感染 [+5]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

117

项与 CCR2 相关的临床试验

NCT06171178 / Recruiting临床1期

A Phase 1, Open-Label, Dose Escalation and Expansion Study of ASP1012, an Oncolytic Virus, in Participants With Locally Advanced or Metastatic Solid Tumors

ASP1012 is a type of virus called an oncolytic virus which is used to treat some cancers.
ASP1012 was changed in a laboratory to infect and kill cancer cells, leaving healthy cells alone. It also makes the cancer cells visible to the immune system which will fight the cancer cells.
Before ASP1012 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This will help find a suitable dose for future studies and check for potential medical problems from the treatment.
In this study, ASP1012 is being tested in humans for the first time. ASP1012 has already been tested in the laboratory and in animals. This is the standard way new potential treatments are developed.
People in this study will be adults whose tumor has either grown outside of the area where it started (locally advanced) or it has spread to other parts of the body (metastatic). They will receive ASP1012. Also, some people will receive ASP1012 with pembrolizumab, an approved medicine.
There are 2 main aims of this study. The first is to learn if people with certain solid tumors can tolerate different doses of ASP1012. The second is to find a suitable dose of ASP1012.
This study will be in 3 parts.
Part 1 is called Dose Escalation. People with locally advanced or metastatic tumors can take part. They will have been previously treated with all available standard cancer therapies. Different small groups of people will receive lower to higher doses of ASP1012.
For each dose, any medical problems will be recorded. This will help to find suitable doses of ASP1012 to use in Parts 2 and 3 of the study. The first group will receive the lowest dose of ASP1012. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP1012. The panel will do this for each group until all groups have taken ASP1012 or until suitable doses have been selected for Parts 2 and 3.
Part 2 is called Dose Expansion. 3 groups will take part: people with previously-treated melanoma (a type of skin cancer) that have not responded to their treatment (refractory) or their cancer has come back (relapsed), people with newly-diagnosed or untreated melanoma, and people with previously-treated solid tumors. People with previously-treated melanoma will receive ASP1012 at the dose worked out from Part 1. People with previously-treated solid tumors will receive ASP1012 with pembrolizumab. The first few people will receive ASP1012 at a lower dose than the dose worked out from Part 1, to check the safety of the treatments being given together. If there are no safety issues: the next people in the solid tumor group will receive ASP1012 at the dose worked out from Part 1, with pembrolizumab; also people with untreated melanoma will receive ASP1012 at the dose worked out from Part
1, with pembrolizumab.
Part 3 is also a Dose Expansion for people with other specific cancers. These are stomach cancer, ovarian cancer, or colorectal cancer. If people with certain tumors respond well in Parts 1 and 2 of the study, other people with this same type of tumor can also take part in Part 3.
For all parts of the study, ASP1012 will be given through a vein. This is called an infusion.
Each treatment cycle is 21 days long. People will start with 3 treatment cycles. People in the study may receive extra treatment cycles, if they respond well to treatment. People with melanoma who are receiving ASP1012 with pembrolizumab will not be offered the extra treatment cycles. People can stop leave the study early if: they have medical problems from the treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; or they do not come back for treatment.
People will visit the clinic on certain days during their treatment. Some visits will be virtual or by phone. During all clinic visits, the study doctors will check for any medical problems from ASP1012. They will also check vital signs. Vital signs include temperature, pulse, breathing rate, the amount of oxygen in the blood, and blood pressure. At some visits, other checks will also include a medical examination, and an electrocardiogram (ECG) to check the heart rhythm, blood draws and urine samples for testing. A tumor sample, if available, will be taken during the first treatment cycle. People will have imaging scans and have blood draws for testing every 6 weeks during and after treatment. This will stop if they leave the study early.
People will visit the clinic within 7 days and 30 days after stopping treatment. At both visits, the study doctors will check for any medical problems from ASP1012. Other checks will include a medical examination, blood draws and urine samples for testing and checking vital signs. An ECG will also be done at the 7-day visit. After the 30-day visit, clinic staff will phone people in the study every 12 weeks to check the condition of their cancer for up to 1 year.

开始日期2024-02-28

申办/合作机构

Astellas Pharma Global Development, Inc.

NCT05630885 / Active, not recruiting临床2期IIT

A Limited-Center, Prospective, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Cenicriviroc Mesylate on Arterial Inflammation in People Living With HIV

The study is being conducted to determine if cenicriviroc mesylate (CVC) will decrease vascular inflammation as measured by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging of the aorta.

开始日期2023-05-30

申办/合作机构

National Institute of Allergy & Infectious Diseases

[+1]

NCT04334915 / Withdrawn临床2期IIT

A Multicenter, Prospective, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of Cenicriviroc Mesylate on Arterial Inflammation in People Living With HIV

The purpose of this study is to evaluate the effects of cenicriviroc mesylate (CVC) on arterial inflammation in people living with HIV.

开始日期2022-11-22

申办/合作机构

National Institute of Allergy & Infectious Diseases

[+1]

100 项与 CCR2 相关的临床结果

登录后查看更多信息

100 项与 CCR2 相关的转化医学

登录后查看更多信息

0 项与 CCR2 相关的专利（医药）

登录后查看更多信息

5,016

项与 CCR2 相关的文献（医药）

2024-04-01·Life science alliance

Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.

Article

作者: Kathryn Wright ; Darryl Jy Han ; Renhua Song ; Kumudika de Silva ; Karren M Plain ; Auriol C Purdie ; Ava Shepherd ; Maegan Chin ; Elinor Hortle ; Justin J-L Wong ; Warwick J Britton ; Stefan H Oehlers

Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish-Mycobacterium marinum infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the tsc1a and cxcl12a/ccl2/ccr2 signalling axes resulting in the suppression of non-tnfa expressing macrophage accumulation at early M. marinum granulomas. Mechanistically, we found a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the cxcl12a/ccl2/ccr2 signalling axis was at the expense of the recruitment of classically activated tnfa-expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to M. marinum infection in zebrafish embryos.

2024-02-29·Heliyon

EPO regulates the differentiation and homing of bone marrow mesenchymal stem cells through Notch1/Jagged pathway to treat pulmonary hypertension.

Article

作者: Kang Li ; Chongyang Shen ; Nianchi Wen ; Yicen Han ; Lu Guo

Purpose:

To investigate whether erythropoietin (EPO) can treat pulmonary arterial hypertension (PAH) in rats by regulating the differentiation and homing of bone marrow mesenchymal stem cells (BMSCs) through Notch1/Jagged signaling pathway.

Materials & methods:

BMSCs were isolated from the bone marrow of 6-week-old male SD rats by whole bone marrow method and identified. BMSCs were treated with 500 IU/mL EPO, and the proliferation, migration, invasion and differentiation ability, and the expression of MMP-2 and MMP-9 protein of BMSCs were detected in vitro. After the establishment of the pulmonary hypertension model in rats, BMSCs were intervened with different concentrations of EPO and injected into the rats through intravenous injection. The levels of TNF-α, IL-1β and IL-6 in lung tissue, the expression of SRY CXCR4, CCR2, Notch1 and Jagged protein in lung tissue, and the levels of TGF-α, vascular endothelial factor (VEGF), IGF-1 and HGF in serum were detected. Immunofluorescence (IF) staining was used to detect the co-localization of CD34.

Results:

EPO promoted the proliferation, migration, and invasion of BMSCs by inhibiting Notch1/Jagged pathway in vitro, and induced BMSCs to differentiate into vascular smooth muscle cells and vascular endothelial cells. EPO inhibited Notch1/Jagged pathway in PAH rats, induced BMSCs homing and differentiation, increased the levels of TGF-α, VEGF, IGF-1 and HGF, and decreased the levels of TNF-α, IL-1β and IL-6.

Discussion & conclusion:

EPO can inhibit the Notch1/Jagged pathway and promote the proliferation, migration, invasion, homing and differentiation of BMSCs to treat pulmonary hypertension in rats in vitro and in vivo.

2024-02-23·Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Chidamide improves gefitinib treatment outcomes in NSCLC by attenuating recruitment and immunosuppressive function of myeloid-derived suppressor cells.

Article

作者: Jinjin Shao ; Zhichao Ye ; Zeren Shen ; Nienwei Liu ; Lijiang Zhang ; Masashi Tachibana ; Zhiqi Xie

Clinical resistance to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) remains a significant challenge. Recent studies have indicated that the number of myeloid-derived suppressor cells (MDSCs) increases following gefitinib treatment, correlating with a poor patient response in NSCLC. Our study revealed that gefitinib treatment stimulates the production of CCL2, which subsequently enhances monocyte (M)-MDSC migration to tumor sites. Chidamide, a selective inhibitor of the histone deacetylase subtype, counteracted the gefitinib-induced increase in CCL2 levels in tumor cells. Additionally, chidamide down-regulated the expression of CCR2 in M-MDSCs, inhibiting their migration. Furthermore, chidamide attenuated the immunosuppressive function of M-MDSCs both alone and in combination with gefitinib. Chidamide also alleviated tumor immunosuppression by reducing the number of M-MDSCs in LLC-bearing mice, thereby enhancing the antitumor efficacy of gefitinib. In conclusion, our findings suggest that chidamide can improve gefitinib treatment outcomes, indicating that MDSCs are promising targets in NSCLC.

项与 CCR2 相关的新闻（医药）

2024-03-22

·药时代

9款药物折戟NASH/MASH领域

回首往昔，2023年算是NASH（后更名为MASH）治疗领域黎明前夕的最后一抹暗夜。这一年，Intercept做出了最终决定，宣告终止奥贝胆酸用于NASH领域的开发。历经十数载的坎坷探索，奥贝胆酸在NASH战场上几经挫折、屡败屡战的研发历程至此画上了句号。令人唏嘘的结果背后，映射的是业界对MASH治疗挑战的困顿挣扎。而奥贝胆酸的无奈退出，不过是整个MASH新药研发领域的一个缩影。2024年的今天，Madrigal的Resmetirom如破晓之光，脱颖而出。多数人都在高歌Resmetirom独占鳌头，抢占了价值百亿美元的庞大市场的同时，也在期望未来MASH治疗领域的繁荣。但毋庸置疑的是，创新药“实力”固然重要，但“运气”也必不能少。正是有了过去无数创新药的前赴后继，才能为后来者奠定“成功基础”。下文，笔者将盘点9款曾经折戟MASH的药物，他们有的戛然而止、有的因换适应症而重焕生机，有的在被收购后被暂时搁置……吉利德：selonsertibselonsertib是一种ASK1抑制剂。ASK1是一种抗纤维化类靶点，可以激活JNK、P38等关键调节蛋白诱发炎症和纤维化。2019年2月，selonsertib用于NASH引起的代偿性肝硬化（F4）患者治疗的III期临床stellar-4研究未达主要终点；两个月后，该药另一项III期临床stellar-3研究（用于NASH引起的桥接性纤维化患者）相继失败。同年12月，吉利德又陆续披露了一项selonsertib联用疗法的II期临床ATLAS研究。在比较ACC抑制剂firsocostat（20mg），FXR激动剂cilofexor （30mg），selonsertib（18mg）以及三者之间两两组合与安慰剂相比对改善纤维化的影响。结果显示，对病人纤维化都没有改善效果。吉利德：SimtuzumabSimtuzumab是一种靶向LOXL2的人源化IgG4单克隆抗体，LOXL2是一种催化胶原蛋白和弹性蛋白共价键形成的赖氨酰氧化酶，在纤维化中具有重要的功能。而疗效不足在抗纤维化药物中比较多见，simtuzumab便在多个II期临床中没有显示积极的疗效。在一项IIb期临床试验中，PSC患者经96周simtuzumab治疗后临床疗效仍不佳，simtuzumab对胶原蛋白含量，纤维化期和门静脉压均无治疗作用。诺华/Conatus：emricasan有一种理论认为，NASH是受伤的肝细胞启动了凋亡程序但未能完成，持续刺激伤口愈合和纤维化的结果。emricasan便是一种含半胱氨酸的天冬氨酸蛋白水解酶抑制剂，可有效降低肝细胞炎症和减少凋亡。2019年6月，Conatus和诺华联合开发的pan-caspase抑制剂emricasan在一个以“改善一级纤维化，NASH不恶化”为终点的IIb临床研究中，低高剂量组的疗效（11.2%/12.3%）比安慰剂组（19%）表现更差。最终，诺华宣布退出合作，emricasan的开发也以失败告终。Ipsen/Genfit：elafibranorelafibranor是一款PPARα/δ激动剂，PPAR与FXR属于同一核受体家族，是胆汁酸形成的转录修饰剂并可调节肝脏炎症和纤维化。2020年5月，elafibranor的III期临床RESOLVE-IT研究宣告失败，结果显示elafibranor治疗72周后，未能达主要终点。elafibranor组138名患者（19.2%）和安慰剂组52名患者（14.7%）达到了NASH缓解且纤维化无恶化的替代终点（P=0.066），关键次要治疗终点（纤维化改善≥1期）也无显著差异。值得一提的是，elafibranor在NASH领域失利后，转战原发性胆汁性胆管炎（PBC）的二线疗法，并于2023年底获FDA受理。Intercept：奥贝胆酸奥贝胆酸是一种口服FXR激动剂，该药于2016年5月被FDA批准用于治疗原发性胆汁性胆管炎（PBC）之后，迅速进入NASH的III期临床，并一度被业界寄予厚望。但由于奥贝胆酸“易引发严重瘙痒症状”这一副作用，极大限制了临床应用。且高剂量奥贝胆酸，还可能导致晚期肝病患者出现肝功能恶化。2018年，奥贝胆酸被FDA授予“黑框警告”；2020年，奥贝胆酸用于治疗NASH引起的肝纤维化上市被拒；2023年，奥贝胆酸又因“代替终点”、“药物性肝损伤”等原因再次被FDA拒之门外。2023年9月，Intercept已同意以约8亿美元价格被Alfasigma收购。NGM Bio：aldaferminaldafermin是一款FGF19类似物，可通过靶向NASH的多种致病途径显著降低肝脏脂肪含量并改善肝功能。2021年5月，aldafermin治疗NASH伴2期或3期肝纤维化（F2/F3）的IIb期临床ALPINE 2/3宣告失败。24周时，患者肝纤维化程度改善≥1期并且NASH没有恶化的主要终点。不过在2023年5月，aldafermin的另一项IIb期临床ALPINE 4研究宣布达到主要终点，即ELF评分（可重复的定量无创肝预后监测）实现统计学意义下降。但关键次要终点（达到肝纤维化程度改善≥1级）并未达到。目前，aldafermin原研公司NGM Bio仅以1.35亿美元的价格被风投公司 The Column Group收购。CymaBay：seladelparseladelpar是一款在研的“first-in-class”口服PPARδ激动剂。2019 年 6 月，seladelpar 治疗NASH的IIb期临床试验未达主要终点，即治疗组患者肝脏脂肪含量（LFC）的减少程度劣于安慰剂组。此外，该试验由于潜在的肝损伤风险而停止试验。虽然Seladelpar在NASH领域遇挫，但参考奥贝胆酸的获批路径，该药却在PBC适应症有所建树。2024年2月12日，CymaBay宣布seladelpar用以二线治疗PBC。同日，CymaBay与吉利德达成合作，后者将以总价值43亿美元收购前者。Enanta：EDP-305EDP-305是一种FXR激动剂，在体外抑制造血干细胞的活化，减少MCD诱导的脂肪性肝炎和肝纤维化。2019年9月，EDP-305的临床IIa（ARGON-1）研究的有效性虽然过了统计学意义的阈值，但奥贝胆酸与耐受性相似：瘙痒。ARGON-1研究中，高剂量组（2.5mg）大约有51%的受试者存在瘙痒，且在高剂量组的所有停药，均是由于中度瘙痒。最终，Enanta决定终止评估 EDP-305 作为单一疗法的ARGON-2 研究和谋求对外授权，不再内部开发。Tobira：cenicriviroccenicriviroc（cvc）是一种新型的、口服的、强效的小分子激动剂，其作用是阻断趋化因子2和5受体（CCR2/CCR5）。cvc最初由Tobira/Takeda原研，其CENTAUR IIb期因未观察到显著的纤维化改善宣告宣告失败。后来，cvc被艾尔建收购继续开展III期试验，目前试验已终止，且结果尚未披露。此外，在另一项在IIb期试验中，cvc与诺华FXR激动剂tropifexor联用方案与tropifexor单药治疗未发现治疗益处。结语自1980年NASH首次命名并提出，关于该领域的新药研发便从未止步。因为长达40年研发无果，众多MNC/Biotech纷纷入场却统统铩羽而归。因此，NASH/MASH便被冠以“研发黑洞”之名，与阿尔兹海默症、RSV等疾病一并成为众多药企眼中“最难啃”的骨头。即便如此，业界仍愿意孜孜不倦投入研发。投资者愿意砸钱，去买个“千万分之一”的成功概率，开发者更是愿意大胆尝试，探索未知。在时光流转之中，MASH、阿尔茨海默病以及RSV等顽疾的治疗领域终于迎来了重要转折点，陆续取得了研发成果。考虑到一款药物从研发到上市平均所需耗时10年之久，每一款成功获批的新药背后，往往是无数同行竞品在研发竞赛中的沉浮与迭代。正所谓：一将功成万骨枯，一药获批“万”药无。封面图来源：123rf版权声明/免责声明本文为汇编文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，观看精彩直播！

临床2期临床3期并购临床结果

2024-03-21

·生物谷

J Exp Clin Cancer Res: 双重阻断IL6和CCR2通路为治疗HPV阴性头颈部鳞状细胞癌提供了新的策略

本研究工作表明，同时阻断IL6和CCR2是增强HPV-HNSCC中NK细胞抗肿瘤活性的潜在方法，为开发更有效的基于免疫治疗的治疗该疾病亚型的方法提供了科学依据。头颈部鳞状细胞癌(HNSCC)是一种起源于头颈部粘膜内鳞状细胞的癌症。它涵盖了一系列在口腔、咽、下咽和喉部等结构中发展的癌症。人类乳头瘤病毒(HPV)已被确定为特定类型HNSCC的危险因素，特别是那些影响口咽部的HNSCC。虽然针对复发性头颈部鳞状细胞癌(HNSCC)的T细胞激活免疫疗法在临床试验中取得了令人印象深刻的结果，但它们在大多数患者中往往无效。NK细胞是免疫治疗干预的潜在靶点。然而，基于莫那利珠单抗的治疗在HNSCC中的挫折突显了另一种治疗方法的必要性，以增强其抗肿瘤活性。图片来源：https://doi.org/10.1186/s13046-024-03002-1 近日，来自埃默里大学的研究者们在J Exp Clin Cancer Res杂志上发表了题为“Combined IL6 and CCR2 blockade potentiates antitumor activity of NK cells in HPV-negative head and neck cancer”的文章，该研究揭示了联合阻断IL6和CCR2增强HPV阴性头颈癌患者NK细胞的抗肿瘤活性。研究者使用单细胞RNA测序(scRNA-seq)和TCGA HNSCC数据集来识别NK细胞中的关键分子改变。具有代表性的人乳头瘤病毒阳性和人乳头瘤病毒阴性人喉鳞状细胞癌细胞株和原位小鼠模型被用于验证生物信息学的发现。用流式细胞仪和免疫荧光法检测免疫细胞的变化。通过scRNA-seq数据和TCGA数据的整合，研究者发现IL-6/IL-6R和CCL2/CCR2信号通路对NK细胞逃避免疫攻击的影响在HPV-HNSCC队列中比HPV+HNSCC队列中更明显。值得注意的是，与单独使用任何一种药物相比，CCR2趋化因子受体拮抗剂RS504393与IL6阻断剂联合使用可产生更显著的抗肿瘤效果，这与HPV-HNSCC中更多激活的NK细胞有关。这些结果表明，双重阻断IL6和CCR2通路有效地增强了HPV阴性HNSCC中NK细胞的抗肿瘤活性，为治疗HPV阴性HNSCC提供了新的策略。机制研究图图片来源：https://doi.org/10.1186/s13046-024-03002-1 结合严格的scRNA-seq和高度临床相关动物模型的实验验证，本研究工作表明，同时阻断IL6和CCR2是增强HPV-HNSCC中NK细胞抗肿瘤活性的潜在方法，为开发更有效的基于免疫治疗的治疗该疾病亚型的方法提供了科学依据。（生物谷 Bioon.com）参考文献： Fan Yang et al. Combined IL6 and CCR2 blockade potentiates antitumor activity of NK cells in HPV-negative head and neck cancer. J Exp Clin Cancer Res. 2024 Mar 12;43(1):76. doi: 10.1186/s13046-024-03002-1.

免疫疗法细胞疗法临床研究

2024-03-20

·GlobeNewswire-Health Care

MediciNova Announces Two Abstracts regarding MN-001 (tipelukast) and MN-002 Accepted for Presentation at the 92nd EAS 2024 Congress, the Annual Meeting of the European Atherosclerosis Society

LA JOLLA, Calif., March 20, 2024 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that two abstracts entitled “STUDY PROTOCOL TO EVALUATE MN-001’S (TIPELUKAST) EFFICACY, SAFETY AND TOLERABILITY IN SUBJECTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD), HYPERTRIGLYCERIDEMIA (HTG) AND TYPE-2 DIABETES MELLITUS (T2DM)” and “MN-002, THE METABOLITE OF MN-001(TIPELUKAST) PROMOTES MACROPHAGE CHOLESTEROL EFFLUX” have been accepted and selected for poster presentation at the 92nd European Atherosclerosis Society (EAS) 2024 Congress to be held May 26-29, 2024. MediciNova’s Chief Medical Officer, Kazuko Matsuda, MD PhD MPH will present the ongoing clinical trial design and objectives, and Dr. Qi Huicheng will present the results of the research to evaluate the mechanism of action of MN-001 (tipelukast) and MN-002 (a major metabolite of MN-001). Presentation details will be disseminated as they become available. Kazuko Matsuda, M.D. Ph.D., M.P.H., Chief Medical Officer, MediciNova, Inc., commented, “We are very pleased that the two presentations were accepted at the EAS 2024 Congress. One presentation is regarding the objectives and design of the ongoing Phase 2 clinical trial enrolling patients with Type 2 diabetes, dyslipidemia, and NAFLD. The other presentation is regarding the mechanism of action of MN-001/MN-002 in lipid metabolism, particularly the effects on cholesterol efflux capacity. This is the outcome from our research collaboration with Professor Takashi Mitsui MD PhD, and Professor Masatsune Ogura MD PhD at Juntendo University to evaluate the mechanism of action of MN-001 in lipid metabolism and metabolic syndrome”. About NAFLD, Type 2 Diabetes Mellitus, and Hypertriglyceridemia NAFLD is considered the hepatic manifestation of metabolic syndrome; studies have reported that 50% of patients with metabolic syndrome also have NAFLD. There is sufficient clinical and epidemiological evidence supporting the assertion that NAFLD is strongly associated with an increased prevalence and incidence of cardiovascular disease, T2DM, chronic kidney disease, and malignancy. The presence of dyslipidemia (hypercholesterolemia, hypertriglyceridemia, or both) is reported in 20 - 80% of NAFLD cases. About MN-001 MN-001 (tipelukast) is a novel, orally bioavailable, small molecule compound thought to exert its effects through several mechanisms to produce its anti-inflammatory and anti-fibrotic activity in preclinical models, including leukotriene (LT) receptor antagonism, inhibition of phosphodiesterases (PDE) (mainly 3 and 4), and inhibition of 5-lipoxygenase (5-LO). The 5-LO/LT pathway has been postulated as a pathogenic factor in fibrosis development, and MN-001's inhibitory effect on 5-LO and the 5-LO/LT pathway is a novel approach to treat fibrosis. MN-001 has been shown to down-regulate expression of genes that promote fibrosis including LOXL2, Collagen Type 1 and TIMP-1. MN-001 has also been shown to down-regulate expression of genes that promote inflammation including CCR2 and MCP-1. In addition, MN-001 was found to inhibit triglyceride synthesis in hepatocytes by inhibiting arachidonic acid uptake. About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety profiles, MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in glioblastoma, Long COVID, and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2023 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT:Geoff O'BrienVice PresidentMediciNova, Inc.info@medicinova.com

临床2期临床3期