更新于：2024-11-01

CCR1

更新于：2024-11-01

基本信息

别名

C-C chemokine receptor type 1、C-C CKR-1、C-C motif chemokine receptor 1

+ [16]

简介

Receptor for a C-C type chemokine. Binds to MIP-1-alpha, MIP-1-delta, RANTES, and MCP-3 and, less efficiently, to MIP-1-beta or MCP-1 and subsequently transduces a signal by increasing the intracellular calcium ions level. Responsible for affecting stem cell proliferation.

关联

项与 CCR1 相关的药物

OV-Cmab-CCL5

靶点

CCR1 x EGFR

作用机制

CCR1调节剂 [+1]

在研机构

City of Hope National Medical Center

原研机构

City of Hope National Medical Center

在研适应症

胶质母细胞瘤

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

CCL3-containing Id vaccines(奥斯陆大学)

靶点

CCR1

作用机制

CCR1拮抗剂

在研机构

University of Oslo

原研机构

University of Oslo

在研适应症

多发性骨髓瘤

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

SSFF-02

靶点

CCR1 x CCR3 x CCR5

作用机制

CCR1拮抗剂 [+2]

在研机构

University of Texas at El Paso

原研机构

University of Texas at El Paso

在研适应症

乳腺癌

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

项与 CCR1 相关的临床试验

NCT02133482 / Withdrawn临床1期

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 639667 in Healthy Male Subjects (Single-blind, Partially Randomised, Placebo-controlled Parallel Group Design)

The primary objective of this trial is to investigate the safety and tolerability of BI 639667 in healthy male subjects following oral administration of single rising doses.
Secondary objectives are the exploration of the pharmacokinetics (PK) including dose proportionality as well as investigation of linearity and pharmacodynamics (PD) of BI 639667 after single dosing and the assessment of the PK/PD relationship.

开始日期2014-07-01

申办/合作机构

Boehringer Ingelheim GmbH

NCT01404585 / Completed临床2期

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BMS-817399 in Adults With Active, Moderate to Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate

The purpose of this study is to assess whether BMS-817399 in combination with Methotrexate is effective in treating moderate to severe rheumatoid arthritis.

开始日期2011-09-01

申办/合作机构

Bristol Myers Squibb Co.

NCT01242917 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety and Efficacy of CCX354-C in Subjects With Rheumatoid Arthritis Partially Responsive to Methotrexate Therapy

This is a randomized, double-blind, placebo-controlled, Phase 2 study to evaluate the safety and efficacy of CCX354-C in subjects with rheumatoid arthritis partially responsive to methotrexate therapy.

开始日期2010-09-01

申办/合作机构

ChemoCentryx, Inc.

100 项与 CCR1 相关的临床结果

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100 项与 CCR1 相关的转化医学

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0 项与 CCR1 相关的专利（医药）

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1,857

项与 CCR1 相关的文献（医药）

2025-02-01·Biomaterials

Programmed surface platform orchestrates anti-bacterial ability and time-sequential bone healing for implant-associated infection

Article

作者: Xi, Yue ; Wang, Ying ; Wang, Yuchen ; Tang, Like ; Chen, Yitong ; Yang, Guoli ; Zhang, Qi ; Lai, Kaichen ; Wang, Zhaolong ; Yu, Zhou ; Tian, Anrong ; Xu, Danyu ; Gao, Changyou ; Huang, Tingben ; Li, Shuangyang ; Wu, Mengjie

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag⁺) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

2024-12-01·International Immunopharmacology

Ccl5 Macrophages drive pro-inflammatory responses and neutrophil recruitment in sepsis-associated acute kidney injury

Article

作者: Wang, Chunli ; Fan, Wenlin ; Liang, Huaping ; Chi, Qingjia ; Xu, Kang

Sepsis leads to dysfunctional immune responses with multi-organ damage, and acute kidney injury (AKI) is a common complication of sepsis. To gain a deeper understanding of the specific underlying mechanisms of sepsis, we investigated the effects of specific macrophages on sepsis. To gain a deeper understanding of the specific underlying mechanisms of sepsis, we investigated the effects of specific macrophages on sepsis. Single-cell sequencing of a mouse model of endotoxemia revealed that sepsis is a common complication of sepsis. Single-cell sequencing of a mouse model of endotoxemia revealed that the emerging macrophage subpopulation Ccl5⁺ Mac was significantly pro-inflammatory, activating a large number of pathways activating a large number of pathways associated with immune response and inflammatory response, including IL6-JAK-STAT3 signaling, TGF-β signaling, and inflammatory response. Interestingly, we found that Ccl5⁺ Mac recruits neutrophil through CCL5-CCR1 ligand receptor pairs by cellular communication analysis thereby further affecting sepsis. We therefore hypothesize that this macrophage subpopulation is actively involved in the underlying molecular mechanisms of AKI. We therefore hypothesize that this macrophage subpopulation is actively involved in the underlying molecular mechanisms of AKI in sepsis and provide valuable insights.

2024-11-21·Journal of Biomolecular Structure and Dynamics

General structure-activity/selectivity relationship patterns for the inhibitors of the chemokine receptors (CCR1/CCR2/CCR4/CCR5) with application for virtual screening of PubChem database

Article

作者: Darsaraee, M. ; Kaveh, S. ; Neiband, M.S ; Mani-Varnosfaderani, A.

CC chemokine receptors (CCRs) form a crucial subfamily of G protein-linked receptors that play a distinct role in the onset and progression of various life-threatening diseases. The main aim of this research is to derive general structure-activity relationship (SAR) patterns to describe the selectivity and activity of CCR inhibitors. To this end, a total of 7332 molecules related to the inhibition of CCR1, CCR2, CCR4, and CCR5 were collected from the Binding Database and analyzed using machine learning techniques. A diverse set of 450 molecular descriptors was calculated for each molecule, and the molecules were classified based on their therapeutic targets and activities. The variable importance in the projection (VIP) approach was used to select discriminatory molecular features, and classification models were developed using supervised Kohonen networks (SKN) and counter-propagation artificial neural networks (CPANN). The reliability and predictability of the models were estimated using 10-fold cross-validation, an external validation set, and an applicability domain approach. We were able to identify different sets of molecular descriptors for discriminating between active and inactive molecules and model the selectivity of inhibitors towards different CCRs. The sensitivities of the predictions for the external test set for the SKN models ranged from 0.827-0.873. Finally, the developed classification models were used to screen approximately 2 million random molecules from the PubChem database, with average values for areas under the receiver operating characteristic curves ranging from 0.78-0.96 for SKN models and 0.75-0.89 for CPANN models.Communicated by Ramaswamy H. Sarma.

项与 CCR1 相关的新闻（医药）

2024-08-26

·生物探索

Immunity | 细胞因子METRNL可通过破坏线粒体功能抑制CD8+T细胞抗肿瘤活性

引言逆转肿瘤浸润淋巴细胞（Tumor-infiltrating lymphocyte, TIL）功能衰退是许多癌症免疫治疗策略的重点，但人们对引发和维持TIL功能减退的条件及其可逆性知之甚少。镍纹蛋白样蛋白（METRNL）是一种因运动或寒冷暴露而分泌的细胞因子，可改善葡萄糖耐量，诱导与米色脂肪产热相关的基因表达，并刺激脂肪组织巨噬细胞的替代激活【1, 2】。METRNL通过AMP激活蛋白激酶（AMPK）或过氧化物酶体增殖物激活受体（PPARδ）【3】增加脂肪酸氧化相关基因和抗炎基因的表达，并通过PPARγ改善胰岛素敏感性【4】。METRNL也由M2极化巨噬细胞分泌在屏障组织中，最近的研究表明巨噬细胞分泌的METRNL可以抑制慢性炎症并促进骨骼和心肌修复【5, 6】，但METRNL是否以及如何在T细胞生物学中发挥作用从未被报道。近日，约翰·霍普金斯大学医学院的Michael Lim团队在Immunity杂志上发表了文章The cytokine Meteorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function，他们证明METRN是肿瘤微环境（TME）中免疫细胞分泌的一种代谢活性细胞因子，可促进TME中TIL功能减退。从机制上讲，METRNL增加了PPARδ活性，导致线粒体去极化和氧化磷酸化减少，从而引发CD8+T细胞代谢向糖酵解转变，其敲除或下调则能改善CD8+T细胞代谢并延缓肿瘤生长，证实靶向METRNL-E2F-PPARδ途径以支持TME中CD8+T细胞功能的治疗潜力。该团队首先对从未经治疗的胶质母细胞瘤（GBM）、前列腺癌（PRAD）、膀胱尿路上皮癌（PRAD）和肾细胞癌（RCC）患者中分离出的TIL和外周血单核细胞（PBMC）进行RNA-seq分析，将METRNL确定所有四种肿瘤类型共有的CD8+TIL和PBMC之间显示出差异表达的基因。随后，他们将分泌METRNL的CD8+T细胞与幼稚CD8+T细胞共培养，发现可引起增殖减少，若利用siRNA抑制Metrnl表达，则能减缓小鼠体内肿瘤进展。除了肿瘤浸润CD8+T细胞外，他们进一步分析了PRAD浸润免疫细胞的单细胞测序数据，确认单核/巨噬细胞和树突状细胞也会表达METRNL，且自分泌和旁分泌信号传导均可对CD8+TIL产生抑制作用。功能障碍线粒体的积累是CD8+TIL特征之一，已知METRNL可调节葡萄糖耐量和线粒体电子传递链等多种代谢过程，于是该团队用线粒体膜电位染料TMRM和示踪染料MitoTracker测定METRNL暴露后T细胞中线粒体结构完整性，结果显示T细胞中MitoTracker染色呈剂量依赖性减少且膜电位遭到破坏，这些变化直接导致ROS累积、DNA双链断裂以及细胞凋亡增加。为进一步了解由此引起的代谢变化，他们在高剂量METRNL暴露后对CD8+T细胞的代谢物进行了液相色谱-质谱分析，与对照组间差异最明显的代谢途径与糖酵解有关，暴露组的糖酵解产物增加。接下来，他们比较了WT和Metrn1-/-CD8+T细胞的差异表达基因，观察到编码T细胞效应细胞因子（Gzma/f/g）、炎症细胞因子（Il-10/13/24/4/5等）、趋化因子受体（Ccr1、Cxcr1）的基因在Metrn1-/-CD8+T细胞中上调。为识别METRNL下游的转录因子，他们使用ISMARA工具重新分析上述RNA-seq数据，发现最显著的差异存在于E2F中，之前的工作已报道E2F、PPARδ和METRNL在缓解骨骼肌胰岛素抵抗中的联系【3】，他们测试了METRNL处理后CD8+T细胞中PPARδ的转录及活性，一方面METRNL处理增加了PPARD表达，但该效果在加入E2F泛抑制剂后被消除，另一方面，他们发现在WT CD8+T细胞中加入PPARδ拮抗剂后，细胞中线粒体呼吸能力呈剂量依赖性增加，提示METRNL通过CD8+T细胞中的E2F-PPARd途径对线粒体呼吸产生影响。模式图（Credit: Immunity）综上，这项工作证明细胞因子METRNL是CD8+T细胞代谢的可逆调节因子，可促进肿瘤微环境中TIL功能减退，因此，可通过靶向METRNL-E2F-PPARδ轴来支持CD8+TIL线粒体功能以发挥抗肿瘤活性。参考文献 1. Li, Z.-Y., Zheng, S.-L., Wang, P., Xu, T.-Y., Guan, Y.-F., Zhang, Y.-J., and Miao, C.-Y. (2014). Subfatin is a novel adipokine and unlike Meteorin in adipose and brain expression. CNS Neurosci. Ther. 20, 344–354. 2. Rao, R.R., Long, J.Z., White, J.P., Svensson, K.J., Lou, J., Lokurkar, I.,Jedrychowski, M.P., Ruas, J.L., Wrann, C.D., Lo, J.C., et al. (2014). Meteorin-like is a hormone that regulates immune-adipose interactionsto increase beige fat thermogenesis. Cell 157, 1279–1291. 3. Jung, T.W., Lee, S.H., Kim, H.C., Bang, J.S., Abd El-Aty, A.M.,Hacımuft € uo € glu, A., Shin, Y.K., and Jeong, J.H. (2018). METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARd-dependent pathways in skeletal muscle of mice. Exp. Mol. Med.50, 1–11. 4. Li, Z.-Y., Song, J., Zheng, S.-L., Fan, M.-B., Guan, Y.-F., Qu, Y., Xu, J.,Wang, P., and Miao, C.-Y. (2015). Adipocyte Metrnl Antagonizes Insulin Resistance Through PPARg Signaling. Diabetes 64, 4011–4022. 5. Reboll, M.R., Klede, S., Taft, M.H., Cai, C.L., Field, L.J., Lavine, K.J.,Koenig, A.L., Fleischauer, J., Meyer, J., Schambach, A., et al. (2022).Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase. Science 376, 1343–1347. 6. Baht, G.S., Bareja, A., Lee, D.E., Rao, R.R., Huang, R., Huebner, J.L.,Bartlett, D.B., Hart, C.R., Gibson, J.R., Lanza, I.R., et al. (2020).Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1mechanism. Nat. Metab. 2, 278–289. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.immuni.2024.07.003 责编|探索君排版|探索君文章来源|“BioArt” End 往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文 Cell | 是什么决定了细胞的大小？热文 Nature | 2024年值得关注的七项技术热文 Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文 CRISPR技术进化史 | 24年Cell综述

免疫疗法

2024-06-23

·AIDD Pro

【第一百三十二期】AI+药物研发领域一周资讯

前言 AIDD Pro 根据国内外各大网站以及人工智能药物设计主流新闻网站及公众号，从 AIDD会议、AIDD招聘，重大科研进展、行业动态、最新报告发布等角度，分析挖掘了每周人工智能辅助药物设计领域所发生的、对领域技术发展产生重大推动作用的事件，旨在帮助 AIDD领域研究人员和业内人士及时追踪最新科研动态、洞察前沿热点。如果您觉得符合以上要求的内容我们有遗漏或者更好建议，欢迎后台留言。科研进展2024年6月21日【抑制剂】J. Chem. Inf. Model. | 靶向Toll样受体7和9的新型小分子双抑制剂的发现2024年6月21日【药物发现】ACS Med. Chem. Lett. | 人工智能/机器学习工具在非洲药物发现中心的持续实施和前瞻性验证2024年6月21日【受体】ACS Pharmacol. Transl. Sci. | 靶向趋化因子受体CCR1细胞内变构结合位点的荧光标记吡咯酮类药物2024年6月20日【靶向蛋白降解】J. Am. Chem. Soc. | 靶向嵌合体的溶酶体Glut1促进靶向蛋白降解2024年6月20日【集成学习】J. Chem. Inf. Model. | DrugSK：用于预测多种疾病药物组合的堆叠集成学习框架2024年6月19日【蛋白质-配体】J. Chem. Inf. Model. | 开放源码力场在蛋白质-配体结合亲和力预测中的现状具体信息，请滑动下方文字 1.【抑制剂】免疫细胞异常分泌促炎细胞因子是炎性疾病的主要原因，如系统性红斑狼疮和类风湿关节炎。toll样受体7 (TLR7)和TLR9被隔离在树突状细胞和巨噬细胞的内体腔室中，与这些疾病的发生和进展密切相关。因此，开发靶向失调内体tlr的药物对于减轻全身性炎症是必要的。在这里，我们运用计算机辅助药物发现的原理，鉴定了一种新的低分子量化合物，TLR抑制化合物10 (TIC10)及其强效衍生物(TIC10g)，它们显示出对TLR7和TLR9信号通路的双重抑制。与TIC10相比，TIC10g对小鼠巨噬细胞系和小鼠骨髓树突状细胞中TLR7-和tlr9介导的促炎细胞因子肿瘤坏死因子-α的分泌表现出更明显的抑制作用，且呈浓度依赖性。虽然TIC10g对TLR3和TLR8的激活有轻微的抑制作用，但对细胞表面tlr (TLR1/2、TLR2/6、TLR4、TLR5)没有影响，说明其对TLR7和TLR9具有选择性。此外，机制研究表明，TIC10g通过直接结合TLR9，干扰CpG DNA对TLR9的激活，抑制下游通路。Western blot分析显示，TIC10g下调活化B细胞核因子κ-轻链增强子p65亚基(NF-κB)和丝裂原活化蛋白激酶(MAPKs)的磷酸化，包括细胞外信号调节激酶、p38-MAPK和c-Jun n-末端激酶。这些发现表明，新的配体TIC10g是内体TLRs (TLR7和TLR9)的特异性双抑制剂，破坏MAPK-和NF-κ b介导的促炎基因表达。链接网址：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acs.jcim.4c00578 DOI：https://doi-org.libproxy1.nus.edu.sg/10.1021/acs.jcim.4c00578 2.【药物发现】人工智能(AI)和机器学习(ML)有望加速药物发现项目。在开普敦大学(UCT)整体药物发现与开发(H3D)中心开发端到端虚拟筛选级联之后，我们报告了在资源受限环境中使用的开源AI/ML工具的持续实施。链接网址：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acsmedchemlett.4c00243 DOI：https://doi-org.libproxy1.nus.edu.sg/10.1021/acsmedchemlett.4c00243 3.【受体】在这项研究中，我们描述了基于结构的第一个荧光配体的发展，靶向CC趋化因子受体1型(CCR1)的细胞内变构结合位点(IABS)，这是一种G蛋白偶联受体(GPCR)，已被作为炎症和免疫疾病的药物靶点。从之前报道的CCR1细胞内变构调节剂开始，设计、合成了四甲基罗丹明(TAMRA)标记的配体，并测试了它们作为荧光示踪剂探测CCR1与IABS结合的适宜性。在这些研究过程中，我们开发了LT166(12)作为一种高度通用的荧光CCR1配体，能够以非放射性和高通量的方式进行无细胞和基于细胞纳米bret的结合研究。除了检测与12直接竞争的细胞内变构配体外，我们还能够监测细胞外拮抗剂的结合，因为它们与12的正合作结合。因此，我们提供了一种简单且无放射性的方法，可以轻松区分与CCR1的IABS结合的配体和细胞外负调节剂。此外，我们应用12鉴定细胞内CCR1抑制的新型化学型，这些化学型对CCR1的结合选择性高于CCR2。对于新发现的细胞内CCR1配体之一(即23)，我们能够在功能水平上证明CCR1优于CCR2的选择性，并证明该化合物抑制基础β-抑制蛋白向CCR1募集，从而作为一种反向激动剂。因此，我们的荧光CCR1配体12代表了未来研究CCR1靶向药理学和药物发现的一个非常有前途的工具。链接网址：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acsptsci.4c00182 DOI：https://doi-org.libproxy1.nus.edu.sg/10.1021/acsptsci.4c00182 4.【靶向蛋白降解】靶向蛋白质降解技术在生物医学领域，特别是在治疗肿瘤和其他蛋白质相关疾病方面具有巨大的潜力。利用分子胶和PROTAC技术降解细胞内蛋白的研究处于领先地位，而通过溶酶体途径降解膜蛋白和细胞外蛋白的研究仍处于临床前阶段。有用靶标的缺乏是技术进步的巨大限制，因此探索新的、潜在有效的靶向溶酶体降解方法至关重要。在这里，我们采用葡萄糖转运蛋白Glut1作为一种创新的溶酶体靶向受体，并设计了Glut1促进溶酶体降解(GFLD)策略。我们通过可逆加成-片段链转移(RAFT)聚合合成了潜在的Glut1配体，并通过生物正交反应获得了抗体-糖低聚物偶联物作为溶酶体靶向蛋白降解分子，用于PD-L1高表达三阴性乳腺癌的治疗。葡萄糖转运体Glut1作为一种溶酶体靶向受体，在未来有可能在更广泛的药物治疗中取得进展。链接网址：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/jacs.4c02463 DOI：https://doi-org.libproxy1.nus.edu.sg/10.1021/jacs.4c02463 5.【集成学习】联合治疗是医学领域不断探索的一个重要方向，其核心目标是提高治疗疗效，减少不良反应，优化临床结果。机器学习技术在改善药物协同作用组合的预测方面具有很大的前景。然而，大多数研究集中在单一疾病导向的协同预测模型或涉及过多的特征类别，这使得对大多数新药的预测具有挑战性。为了解决这些挑战，开发了DrugSK综合模型，该模型利用SMILES-BERT从3492种药物中提取结构信息，并从48,756种药物组合中训练反应。DrugSK是一个集成的学习模型，能够预测各种药物类别之间的相互作用。首先，从初始数据集训练主学习者。选择随机森林、支持向量机和XGboost模型作为主要学习器，逻辑回归作为次要学习器。然后“生成”一个新的数据集来训练2级学习者，这可以被认为是对每个模型的预测。最后，使用逻辑回归对结果进行过滤。此外，还对新型抗菌药物draflo沙星与其他抗菌药物的联用进行了试验。证实了曲洛沙星与依沙唑对白色念珠菌的协同作用，为皮肤感染的临床治疗提供了启示。DrugSK的预测在实际应用中是准确的，也可以预测结果的概率。此外，还发现曲洛沙星与抗真菌药物有协同作用的趋势。DrugSK的发展将为预测药物联合协同效应提供新的蓝图。链接网址：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acs.jcim.4c00296 DOI：https://doi-org.libproxy1.nus.edu.sg/10.1021/acs.jcim.4c00296 6.【蛋白质-配体】在药物发现中，结合亲和力的计算机预测是优先合成化合物的主要手段之一。基于分子动力学(MD)模拟的炼金术相对结合自由能(RBFE)计算是目前对化合物进行精确亲和力排序的一种流行方法。MD模拟依赖于经验力场参数，这对预测亲和力的准确性有很大影响。在这里，我们评估了六种不同的小分子力场预测实验蛋白质-配体结合亲和力的能力，并对598个配体和22个蛋白质靶点进行了RBFE计算。公共力场OpenFF Parsley和Sage、GAFF和CGenFF的准确性相当，而OPLS3e的准确性要高得多。然而，使用Sage、GAFF和CGenFF的共识方法可导致与OPLS3e相当的准确性。虽然Parsley和Sage在整个数据集的汇总统计数据上表现相当，但在异常值方面存在差异。对力场的分析表明，改进的参数导致对涉及这些参数的数据集子集的亲和预测的准确性显着提高。较低的精度不仅与力场参数有关，还与输入准备和计算的采样收敛性有关。特别是大的扰动和非收敛的模拟导致不太准确的预测。输入结构、gromac力场文件以及分析Python笔记本都可以在GitHub上获得。链接网址：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acs.jcim.4c00417 DOI：https://doi-org.libproxy1.nus.edu.sg/10.1021/acs.jcim.4c00417 上下滚动查看更多药企动态2024年6月21日【阿斯利康】阿斯利康「奥希替尼」在华申报第5项适应症2024年6月21日【和黄医药】10多年来首款！和黄医药/武田呋喹替尼在欧盟获批2024年6月20日【强生】强生向FDA递交「古塞奇尤单抗」皮下注射剂治疗克罗恩病上市申请2024年6月20日【诺诚健华】诺诚健华CD19单抗「坦昔妥单抗」申报上市2024年6月19日【迪哲医药】全球首创！迪哲医药戈利昔替尼获批2024年6月19日【赛诺菲】赛诺菲每周1次血友病A疗法在欧盟获批上市各动态具体信息，请滑动下方文字 1.【阿斯利康】 6月21日，CDE网站显示，阿斯利康的奥希替尼新适应症上市申请正式获得受理，根据临床试验进展，推测本次申报上市新适应症为：用于在接受含铂根治性放化疗后未出现疾病进展、具有表皮生长因子受体（EGFR）外显子19缺失（Ex19del）或外显子21（L858R）置换突变的局部晚期不可切除(III期)非小细胞肺癌（NSCLC）成人患者的治疗。链接网址请戳我 2.【和黄医药】 6月21日，和黄医药宣布，合作伙伴武田已收到欧盟委员会（EC）的通知，该公司已批准Fruzaqla(呋喹替尼)上市，单药用于治疗先前接受过现有标准疗法治疗的转移性结直肠癌(mCRC)成年患者，这些标准疗法包括基于氟嘧啶、奥沙利铂和伊立替康的化疗、抗VEGF药物和抗EGFR药物，以及经曲氟尿苷嘧啶或瑞戈非尼治疗后疾病进展或不耐受的患者。呋喹替尼是欧盟十多年来首个针对mCRC的新型靶向疗法，无论患者的生物标志物状态如何。链接网址请戳我 3.【强生】 6月20日，强生宣布古塞奇尤单抗（商品名：Tremfya）皮下注射（SC）剂型诱导治疗中重度活动性克罗恩病（CD）成年患者的III期GRAVITI研究取得了积极结果。基于该研究和两项头对头III期研究（GALAXI 2和GALAXI 3）的积极结果，强生已向FDA递交古塞奇尤单抗治疗CD的上市申请。链接网址请戳我 4.【诺诚健华】 6月20日，诺诚健华宣布国家药监局（NMPA）已受理CD19单抗坦昔妥单抗（tafasitamab）联合来那度胺治疗不适合自体干细胞移植条件的复发/难治弥漫性大B细胞淋巴瘤（DLBCL）成人患者的生物制品上市许可申请（BLA），并纳入优先审评。链接网址请戳我 5.【迪哲医药】 6月19日，据国家药监局官网，迪哲医药高选择性JAK1抑制剂戈利昔替尼（商品名为高瑞哲）获批，用于治疗复发难治性外周T细胞淋巴瘤（r/r PTCL）。高瑞哲成为“全球首个且唯一”针对PTCL的JAK1抑制剂，也是过去十年来，该治疗领域上市的首个创新药。链接网址请戳我 6.【赛诺菲】 6月19日，Sobi宣布，其与赛诺菲共同开发的Altuvoct（efanesoctocog alfa）已经获得欧盟委员会（EC）批准上市，用于血友病A成人和儿童患者的常规预防性治疗和按需治疗，以控制出血事件，以及围手术期管理（手术）。链接网址请戳我上下滚动查看更多会议信息 2024年6月27-28日上海求实医药咨询有限公司举办ING 2024第七届免疫及基因治疗论坛2024年8月29-30日上海求实医药咨询有限公司举办ICNS 2024 第四届中枢神经系统药物深度聚焦论坛各会议具体详情和参会方式，请滑动下方文字 ING 2024第七届免疫及基因治疗论坛主办方：上海求实医药咨询有限公司会议时间：2024年6月27日-28日会议地点：北京会议主旨：聚焦CGT领域开发的核心问题，破除技术壁垒，推动产业不断前进，开启生物医药产业下一个风口！链接网址请戳我 ICNS 2024 第四届中枢神经系统药物深度聚焦论坛主办方：上海求实医药咨询有限公司会议时间：2024年8月29日-30日会议地点：南京会议主旨：深化基础研究，提升药物开发成功率，突破技术瓶颈，并探索新疗法的前沿进展。链接网址请戳我上下滚动查看更多版权信息本文内容均由小编收集于公开的各个网络平台，发布的目的仅为了方便大家一站式了解AIDD行业信息，并未对发布源头进行真实性验证。如您发现相关信息有任何版权侵扰或者信息错误，请及时联系AIDD Pro（请添加微信号sixiali_fox59）进行删改处理。原创内容未经授权，禁止转载至其他平台。有问题可发邮件至sixiali@stonewise.cn 关注我，更多资讯早知道↓↓↓

临床1期

2024-02-20

·BioSpace

Lumicell Announces Initial Data Demonstrating LUMISIGHT™’s Ability to Detect Tumors Metastasized to Multiple Organs in the Peritoneum

Promising feasibility study results for imaging technology that identified malignant peritoneal tumor metastasis during surgery NEWTON, Mass.--(BUSINESS WIRE)-- Lumicell Inc., a privately held company focused on innovative fluorescence-guided imaging technologies for cancer surgery, today announced promising initial data from its ongoing feasibility study for lead candidate LUMISIGHT™ to detect peritoneal malignancies during surgical debulking. The ongoing study is utilizing the investigational LUMISIGHT optical imaging drug and accompanying imaging device to distinguish tumor metastases to organs within the peritoneum. The initial results from adult patients were shared in a podium presentation by James C. Cusack, Jr. MD, Associate Professor of Surgery at Massachusetts General Hospital, at the Advanced Cancer Therapies meeting organized by the Society of Surgical Oncology. “This data advances the potential for image-guided surgery to detect small tumors and metastases to organs in the peritoneal cavity which could provide better outcomes for our patients,” said Dr. Cusack. “Further innovation is desperately needed to improve the benefits of cytoreductive surgery for this invasive and elusive cancer. We look forward to continuing the clinical development program with Lumicell and advancing patient care.” The presence of peritoneal metastases has a significant negative impact on survival for patients. One of the most important determinants of treatment success and long-term overall survival is the ability to achieve removal of all visible cancer during initial surgery prior to the heated chemotherapy for a complete cytoreduction.2-5 “We are highly encouraged by this initial data in a promising new indication, as we continue to expand the development of LUMISIGHT across the spectrum of solid tumors. Everything we do at Lumicell is focused on improving surgical outcomes for patients,” said Howard Hechler, President of Lumicell. About Peritoneal Surface Malignancies and Metastasis Peritoneal surface malignancies include primary peritoneal malignant mesothelioma and tumors that have spread from different organs, referred to as peritoneal metastases. These metastases can originate from organs such as appendiceal, colorectal, gastric, pancreatic, and ovarian cancers, and affect more than 75,000 patients each year in the United States.1 The presence of disease and the extent of disease are often difficult to be fully evaluated by conventional non-invasive imaging techniques such as CT scan, PET scan, or MRI. Small peritoneal surface nodules are often detected at the time of surgical exploration by the surgeon’s eyes versus conventional imaging techniques. One of the most important determinants of treatment success and overall survival is the ability to achieve complete cytoreduction (CCR).2-5 While patients with no residual disease (CCR0) or minimal residual peritoneal surface tumor nodules less than 2.5 mm in maximum diameter (CCR1) have significantly better survival than those with residual nodules more than 2.5 mm in maximum diameter (CCR2), patients with CCR0 have experienced the best clinical outcomes.2,3,5 About Lumicell, Inc. Lumicell is a privately held company focused on the development and commercialization of innovative fluorescence-guided technologies for cancer surgery with the potential to improve patient outcomes and reduce healthcare costs. The company’s first products pending approval are LUMISIGHT™ and the Lumicell™ Direct Visualization System which, in combination, are designed to illuminate cancerous tissue during initial surgery potentially reducing the frequency of repeat surgeries. LUMISIGHT and the Lumicell Direct Visualization System are investigational products, both limited by federal law to investigational use only and are not commercially available. These products are currently under FDA review for their first indication in breast conserving surgery; and are also being explored across a wide variety of solid tumor indications to enhance the standard of care treatment by guiding the resection of additional cancer that may have otherwise been left behind. For more information, please visit or follow us at LinkedIn and X. Foster, J.M., Zhang, C., Rehman, S., Sharma, P. and Alexander, H.R. (2023), The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. CA A Cancer J Clin, 73: 49-71. Elias, D., F. Quenet, and D. Goere, Current status and future directions in the treatment of peritoneal dissemination from colorectal carcinoma. Surg Oncol Clin N Am, 2012. 21(4): p. 611-23. Glockzin, G. and P. Piso, Current status and future directions in gastric cancer with peritoneal dissemination. Surg Oncol Clin N Am, 2012. 21(4): p. 625-33. Helm, C.W., Current status and future directions of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer. Surg Oncol Clin N Am, 2012. 21(4): p. 645-63. Votanopoulos, K.I., et al., Current status and future directions in appendiceal cancer with peritoneal dissemination. Surg Oncol Clin N Am, 2012. 21(4): p. 599-609. Chan, C.H., et al., Preclinical Evaluation of Cathepsin-Based Fluorescent Imaging System for Cytoreductive Surgery. Ann Surg Oncol, 2017. 24(4): p. 931-938.

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