更新于：2024-11-01

CACNG1

更新于：2024-11-01

基本信息

别名

CACNG1、CACNLG、calcium channel, voltage-dependent, gamma subunit 1

+ [3]

简介

Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics.

关联

抗CACNG1抗体-DMPK siRNA偶联物(再生元)

靶点

CACNG1 x DMPK

作用机制

CACNG1阻滞剂 [+1]

在研机构

Regeneron Pharmaceuticals, Inc.

原研机构

Regeneron Pharmaceuticals, Inc.

在研适应症

肌肉骨骼系统疾病

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

WO2024098002

专利挖掘

靶点

CACNG1

作用机制-

在研机构

Regeneron Pharmaceuticals, Inc.

原研机构

Regeneron Pharmaceuticals, Inc.

在研适应症

遗传病与畸形 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

Diltiazem Malate

苹果酸地尔硫卓

靶点

CACNG1

作用机制

CACNG1阻滞剂

在研机构-

原研机构

Merck & Co., Inc.

在研适应症-

非在研适应症

心绞痛 [+5]

最高研发阶段撤市

首次获批国家/地区

美国

首次获批日期1996-10-04

项与 CACNG1 相关的临床试验

NCT06534671 / Enrolling by invitation临床4期IIT

Diltiazem in Jervell and Lange-Nielsen Syndrome

This study will test the effect of diltiazem, a calcium channel blocking drug, on the QT interval in patients with Jervell and Lange-Nielsen syndrome. This will be a single IV dose and acute effects (within minutes) will be observed.

开始日期2024-10-16

申办/合作机构

Vanderbilt University Medical Center

IRCT20210519051345N53 / RecruitingIIT

Fasted-state in vivo bioequivalence study of Diltiazem 60 mg tablet manufactured by MehrDarou compared with innovator product

开始日期2024-04-13

申办/合作机构

Tabriz University of Medical Sciences

CTRI/2023/09/057330 / Recruiting临床4期

Efficacy and safety of Murivenna anal infiltration compared to Diltiazem topical application in chronic anal fissure: A prospective randomized open-label clinical trial - CAF

开始日期2023-09-07

申办/合作机构

Central Council For Research In Ayurvedic Sciences

100 项与 CACNG1 相关的临床结果

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100 项与 CACNG1 相关的转化医学

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0 项与 CACNG1 相关的专利（医药）

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118

项与 CACNG1 相关的文献（医药）

2023-07-25·Schizophrenia (Heidelberg, Germany)

Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients.

Article

作者: Wang, Xueping ; Lu, Zhe ; Yue, Weihua ; Sun, Yaoyao ; Zhang, Yuyanan ; Lu, Tianlan ; Yan, Hao ; Mei, Dongli

Aripiprazole is recommended for routine use in schizophrenia patients. However, the biological mechanism for the adverse drug reactions (ADRs) among schizophrenia patients with the antipsychotic drug aripiprazole is far from clear. To explore the potential genetic factors that may cause movement-related adverse antipsychotic effects in patients, we conducted an association analysis between movement-related ADRs and SNPs in schizophrenia patients receiving aripiprazole monotherapy. In this study, multiple ADRs of 384 patients were quantified within 6-week treatment, and the scores of movement-related ADRs at baseline and follow-up time points during treatment were obtained. The highest score record was used as the quantitative index in analysis, and genetic analysis at the genome-wide level was conducted. The SNP rs4149181 in SLC22A8 [P = 2.28 × 10^-8] showed genome-wide significance, and rs2284223 in ADCYAP1R1 [P = 9.76 × 10^-8], rs73258503 in KCNIP4 [P = 1.39 × 10^-7], rs678428 in SMAD9 [P = 4.70 × 10^-7], rs6421034 in NAP1L4 [P = 6.80 × 10^-7], and rs1394796 in ERBB4 [P = 8.60 × 10^-7] were found to be significantly associated with movement-related ADRs. The combined prediction model of these six loci showed acceptable performance in predicting adverse events [area under the curve (AUC): 0.84]. Combined with the function and network of the above genes and other candidate loci (KCNA1, CACNG1, etc.), we hypothesize that SLC22A8 and KCNIP4-Kv channel perform their respective functions as transporter or channel and participate in the in vivo metabolism or effects of aripiprazole. The above results imply the important function of ion transporters and channels in movement-related adverse antipsychotic effects in aripiprazole monotherapy schizophrenia patients.

2022-05-01·Protein Science4区 · 生物学

Molecular interactions of STAC proteins with skeletal muscle dihydropyridine receptor and excitation‐contraction coupling

4区 · 生物学

Article

作者: Oakley, Aaron J. ; Sundararaj, Srinivasan ; Rowland, Emily ; Aditya, Shouvik ; Casarotto, Marco G. ; Dulhunty, Angela F. ; Shishmarev, Dmitry

AbstractExcitation‐contraction coupling (ECC) is the physiological process in which an electrical signal originating from the central nervous system is converted into muscle contraction. In skeletal muscle tissue, the key step in the molecular mechanism of ECC initiated by the muscle action potential is the cooperation between two Ca2+ channels, dihydropyridine receptor (DHPR; voltage‐dependent L‐type calcium channel) and ryanodine receptor 1 (RyR1). These two channels were originally postulated to communicate with each other via direct mechanical interactions; however, the molecular details of this cooperation have remained ambiguous. Recently, it has been proposed that one or more supporting proteins are in fact required for communication of DHPR with RyR1 during the ECC process. One such protein that is increasingly believed to play a role in this interaction is the SH3 and cysteine‐rich domain‐containing protein 3 (STAC3), which has been proposed to bind a cytosolic portion of the DHPR α1S subunit known as the II–III loop. In this work, we present direct evidence for an interaction between a small peptide sequence of the II–III loop and several residues within the SH3 domains of STAC3 as well as the neuronal isoform STAC2. Differences in this interaction between STAC3 and STAC2 suggest that STAC3 possesses distinct biophysical features that are potentially important for its physiological interactions with the II–III loop. Therefore, this work demonstrates an isoform‐specific interaction between STAC3 and the II–III loop of DHPR and provides novel insights into a putative molecular mechanism behind this association in the skeletal muscle ECC process.

2018-10-03·Cancer Biology & Therapy3区 · 医学

Clinical and molecular predictors of long-term response in HER2 positive metastatic breast cancer patients

3区 · 医学

Article

作者: Moscetti, Luca ; Conte, Pier Franco ; Cascinu, Stefano ; Guaitoli, Giorgia ; Caggia, Federica ; Bettelli, Stefania ; Piacentini, Federico ; Manfredini, Samantha ; Toss, Angela ; Caprera, Cecilia ; Cortesi, Laura ; Maiorana, Antonino ; Kaleci, Shaniko ; Omarini, Claudia

BACKGROUNDHER2+ metastatic breast cancer (MBC) is a poor prognosis disease, unusually curable. To date, no predictive factors have been clearly correlated with long-term response to anti-HER2 agents.METHODS54 HER2+ MBC patients treated with HER2 targeted therapy as first line treatment were analysed: 40 with a time to progression longer than 3 years in Long Responders (LR) group and 14 with a progression disease within one year of anti-HER2 therapy in a control group named Early Progressors (EP). The expression of 770 genes and 13 molecular pathways were evaluated using Nanostring PanCancer pathway panel performed on FFPE BC tissues.RESULTSConsidering baseline patients and tumor characteristics, EP women had more CNS spread and more metastatic burden of disease compared to LR (p > 0.05). Gene expression analysis identified 30 genes with significantly different expression in the two cohorts; five were driver genes (BRCA1, PDGFRA, AR, PHF6 and MSH2). The majority of these genes were over-expressed, mainly in LR patients, and encoded growth factors, pro- or anti-inflammatory interleukins and DNA repair factors. Only four genes were down regulated, all in EP group (TNFSF10, CACNG1, IL20RB and BRCA1). Most of these genes were involved in MAPK and PI3K pathways. MAPK pathway was differently expressed between LR and EP (p = 0.05). PI3K was the only pathway overexpressed in EP patients.CONCLUSIONSWhole genome expression analysis comparing LR vs. EP identified a group of genes that may predict more favourable long-term outcomes. Up-regulation of MAPK and down-regulation of PI3K pathway could be a positive predictive factors. Further clinical implications are warranted.ABBREVIATIONSBC: breast cancer; MBC: metastatic breast cancer; LR: long responder; EP: early progressor; FFPE: formalin-fixed paraffin-embedded; CNS: central nervous system; PFS: progression free survival; OS: overall survival.

项与 CACNG1 相关的新闻（医药）

2023-09-20

·药明康德

目标“改变基因编辑领域”！再生元打算这么做…

2017年美国FDA批准首个基因疗法Kymriah（tisagenlecleucel）用以急性淋巴细胞白血病（ALL）治疗以来，基因疗法领域在近年不断有所突破。然而尽管该领域持续进展，关于如何将基因载体有效率地递送至肝脏以外的器官与组织以扩大基因疗法的应用范围，一直是产业面对的挑战也是基因疗法领域突破的关键。对此，再生元（Regeneron）发现一项简单的方式——将抗体与病毒载体相连以靶向目标器官——或许是战胜递送挑战直接、有效的方式。无论是直接使用病毒还是脂质纳米颗粒，基因载体在体内的递送最终多聚集在人体的清除器官——肝脏——当中。若是为了增加抵达肝脏以外靶器官的基因载体数量而提高剂量，常常会导致肝脏负荷过重而造成病患因肝毒性而死亡。因此基因疗法的开发目前多集中于那些肝细胞中异常表达的基因，例如靶向PCSK9以降低胆固醇。又例如目前美国FDA正在审评的镰状细胞CRISPR基因编辑疗法，通过使用接近移植手术的离体过程来避免递送问题。凭着其在抗体领域多年来累积的专业知识与经验，再生元正在进行早期研究，打算将抗体连接于标准病毒载体之上，以促进载体专一性地进入特定细胞当中。目前该公司专注于开发靶向肌肉细胞与脑部的疗法，这些疗法目前展现积极的临床前数据。其中最先进的项目是一种针对肌肉细胞中名为CACNG1的蛋白质抗体附着到病毒载体上。根据今年美国基因与细胞治疗学会（ASGCT）会议上公布的数据，该疗法在小鼠和非人类灵长类动物的研究显示，与未经修饰的病毒相比，载体到达肌肉细胞的能力大幅增强，但进入肝脏和心脏的能力却大幅下降。 “我们相信我们已经成为该领域的领导者，”再生元的首席科学官George Yancopoulos博士在接受行业媒体Endpoints采访，谈到这一类疗法时说道。“我们希望宣布使用生物制品来递送基因有效载荷的计划，我们认为这有机会真正继续改变基因疗法领域。” 其实将抗体与病毒载体相连以促进其靶向递送这个想法早在1990年代时就有学者提出，并在临床前研究中展现一定程度的成功。然而阻碍此类疗法被实际应用在人体治疗的瓶颈便是大量生产的挑战。产业界必须能够说服监管单位其具备能力，可将大量生产中每个批次的药物，其抗体与病毒载体的偶联效率保有一致性，使得每个批次药物具备相当的治疗效果。而这也是再生元开发此类疗法时所面对的主要挑战。对于再生元的早期结果，加州大学伯克利分校的生物工程研究员David Schaffer博士称之“有趣”，但在一封电子邮件中指出，“在技术上要实现可重复且稳健的规模化生产可能具有挑战性。” 然而再生元对此疗法的开发信心满满，再生元的基因疗法团队共同负责人Christos Kyratsous博士表示，他们正在推进两种将抗体附着在病毒上的方法，并在这两类方法上看见一致的结果。此外，再生元的领导者也指出他们在大规模生产抗体和不断扩大的腺相关病毒（AAV）载体团队方面的经验。“我们正在走向临床规模的病毒生产。”再生元基因药物部门执行董事Leah Sabin博士说道。让我们期待再生元能够在基因递送挑战上早日做出推进可应用于临床的实质突破，以扩大基因疗法的应用范围，造福广大患者。参考资料：[1] In the Lab: Regeneron brings its antibody chops to gene editing's biggest problem, aiming to 'change the field'. Retrieved September 18, 2023 from https://endpts.com/regeneron-brings-its-antibody-chops-to-gene-editings-biggest-problem/ [2] FDA approval brings first gene therapy to the United States. Retrieved September 18, 2023 from https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states [3] FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease. Retrieved September 18, 2023 from https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-targeted-rna-based-therapy-treat-rare-disease 内容来源于网络，如有侵权，请联系删除。