更新于：2024-11-01

CACNG8

更新于：2024-11-01

基本信息

别名

CACNG6、CACNG8、calcium voltage-gated channel auxiliary subunit gamma 8

+ [4]

简介

Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits.

关联

项与 CACNG8 相关的药物

CERC-611

靶点

CACNG8

作用机制

CACNG8 inhibitors

在研机构

ES Therapeutics Australia Pty Ltd

原研机构

Eli Lilly & Co. [+1]

在研适应症

特发性震颤 [+1]

非在研适应症

疼痛 [+1]

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

11C-TARP-2105

碳[11C]TARP-2105

靶点

CACNG8

作用机制

CACNG8 inhibitors

在研机构

南方科技大学 [+2]

原研机构

The General Hospital Corp.

在研适应症

中枢神经系统疾病

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

JNJ-64140284

靶点

CACNG8

作用机制

CACNG8 inhibitors

在研机构-

原研机构

Johnson & Johnson

在研适应症-

非在研适应症-

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与 CACNG8 相关的临床试验

NCT05234762 / Recruiting临床2期

A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of ES-481 in Adult Patients With Essential Tremors

This Pilot Phase 2A study will investigate the safety, tolerability, and pharmacokinetics (PK) of ES-481 in adult patients with essential tremor.

开始日期2021-11-21

申办/合作机构

ES Therapeutics Australia Pty Ltd

NCT04737174 / Withdrawn临床2期

Adjunctive ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors

Phase 2A single-arm exploratory clinical study in up to 12 adult subjects aged 18 and older with primary glioma, IDH1 mutation, and uncontrolled focal-onset seizure activity to determine the potential efficacy, safety and pharmacokinetics of ES-481 as adjunctive therapy in glioma-associated epilepsy and to assess for potential anti-tumorigenic effects.

开始日期2021-03-25

申办/合作机构

ES Therapeutics Australia Pty Ltd

ACTRN12621000033842 / Recruiting临床2期

A Phase 2A, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of ES-481 in Adult Patients with Drug Resistant Epilepsy.

开始日期2021-01-29

申办/合作机构

ES Therapeutics Australia Pty Ltd

100 项与 CACNG8 相关的临床结果

登录后查看更多信息

100 项与 CACNG8 相关的转化医学

登录后查看更多信息

0 项与 CACNG8 相关的专利（医药）

登录后查看更多信息

项与 CACNG8 相关的文献（医药）

2024-09-19·Cells

Cannabinol (CBN) Influences the Ion Channels and Synaptic-Related Genes in NSC-34 Cell Line: A Transcriptomic Study.

Article

作者: Trainito, Alessandra ; Gugliandolo, Agnese ; D'Angiolini, Simone ; Salamone, Stefano ; Muscarà, Claudia ; Chiricosta, Luigi ; Mazzon, Emanuela ; Pollastro, Federica

Neurological disorders such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and schizophrenia are associated with altered neuronal excitability, resulting from dysfunctions in the molecular architecture and physiological regulation of ion channels and synaptic transmission. Ion channels and synapses are regarded as suitable therapeutic targets in modern pharmacology. Cannabinoids have received great attention as an original therapeutic approach for their effects on human health due to their ability to modulate the neurotransmitter release through interaction with the endocannabinoid system. In our study, we explored the effect of cannabinol (CBN) through next-generation sequencing analysis of NSC-34 cell physiology. Our findings revealed that CBN strongly influences the ontologies related to ion channels and synapse activity at all doses tested. Specifically, the genes coding for calcium and potassium voltage-gated channel subunits, and the glutamatergic and GABAergic receptors (Cacna1b, Cacna1h, Cacng8, Kcnc3, Kcnd1, Kcnd2, Kcnj4, Grik5, Grik1, Slc17a7, Gabra5), were up-regulated. Conversely, the genes involved into serotoninergic and cholinergic pathways (Htr3a, Htr3b, Htr1b, Chrna3, Chrnb2, Chrnb4), were down-regulated. These findings highlight the influence of CBN in the expression of genes involved into ion influx and synaptic transmission.

2024-06-01·Pharmacological Research

Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Article

作者: Zhang, Shunfen ; Zhang, Hongfu ; Chen, Liang ; Lv, Huiyuan ; Zhong, Ruqing ; Tang, Shanlong ; Liu, Zhengqun ; Cai, Xueying

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

2024-03-15·ChemBioChem

Preclinical Evaluation of Azabenzimidazole‐Based PET Radioligands for γ‐8 Dependent Transmembrane AMPA Receptor Regulatory Protein Imaging

Article

作者: Yu, Qingzhen ; Yuan, Hongjie ; Liang, Steven ; Zhou, Xin ; Bi, Chunyang ; Rong, Jian ; Song, Zhendong ; Chaudhary, Ahmad F ; Zhao, Chunyu ; Chen, Jiahui ; Zhang, Kuo ; Collier, Lee ; Li, Yinlong ; Haider, Ahmed ; Patel, Jimmy S ; Davenport, April T ; Daunais, James B ; Zhang, Wei

AbstractAMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ‐8 subunit is enriched and serves as a target for emerging anti‐epileptic drugs. To enable in vivo visualization of TARP γ‐8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel 18F‐labeled TARP γ‐8 inhibitors and their corresponding precursors, stemming from the azabenzimidazole scaffold. The resulting radioligands [18F]TARP‐2204 and [18F]TARP‐2205 were successfully synthesized with acceptable radiochemical yield, high molar activity, and excellent radiochemical purity. In vitro autoradiography demonstrates high level of specific binding of [18F]TARP‐2205 to TARP γ‐8 in both rat and nonhuman primate brain tissues. However, unexpected radiodefluorination in PET imaging studies of rodents emphasizes the need for further structural refinement. This work serves as an excellent starting point for the development of future 18F‐labeled TARP γ‐8 PET tracers, offering valuable insights into medicinal chemistry design, radiosynthesis and subsequent PET evaluation.