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更新于：2025-05-07

CSNK2A2

更新于：2025-05-07

基本信息

别名

casein kinase 2 alpha 2、casein kinase 2 alpha'、casein kinase 2, alpha prime polypeptide

+ [6]

简介

Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:30898438). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:11704824, PubMed:16193064, PubMed:30898438). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387551, PubMed:19387552). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage (PubMed:12631575, PubMed:19387551, PubMed:19387552). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation (PubMed:11239457). Phosphorylates a number of DNA repair proteins in response to DNA damage, such as MDC1, RAD9A, RAD51 and HTATSF1, promoting their recruitment to DNA damage sites (PubMed:20545769, PubMed:21482717, PubMed:22325354, PubMed:26811421, PubMed:30898438, PubMed:35597237). Can also negatively regulate apoptosis (PubMed:19387551, PubMed:19387552). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:12631575, PubMed:19387551, PubMed:19387552). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:12631575, PubMed:19387551, PubMed:19387552). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (PubMed:12631575, PubMed:19387551, PubMed:19387552). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB (PubMed:12631575, PubMed:19387551, PubMed:19387552). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (PubMed:19387550). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:19387549). Acts as an ectokinase that phosphorylates several extracellular proteins (PubMed:12631575, PubMed:19387551, PubMed:19387552). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (PubMed:12631575, PubMed:19387551, PubMed:19387552). May phosphorylate histone H2A on 'Ser-1' (PubMed:38334665).

关联

项与 CSNK2A2 相关的药物

WO2024112731

专利挖掘

靶点

CK2 x CSNK2A2

作用机制-

在研机构

The Salk Institute for Biological Studies

原研机构

The Salk Institute for Biological Studies

在研适应症

心血管疾病 [+5]

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

100 项与 CSNK2A2 相关的临床结果

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100 项与 CSNK2A2 相关的转化医学

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0 项与 CSNK2A2 相关的专利（医药）

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241

项与 CSNK2A2 相关的文献（医药）

2024-05-01·Neural regeneration research

Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation.

Article

作者: Ng, Tsz Kin ; Chen, Shaowan ; Yao, Shi-Qi ; Chu, Wai Kit ; Wang, Yuhang ; Liang, Jia-Jian ; Xu, Yanxuan ; Cui, Qi ; Wang, Meng ; Cen, Ling-Ping ; Huang, Yao

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma, the leading cause of irreversible blindness. We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury. To investigate the underlying mechanism, in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor (4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) by intravitreal injection. We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-¹H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages. Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors. Furthermore, casein kinase-2 inhibition downregulated the expression of genes (Cck, Htrsa, Nef1, Htrlb, Prph, Chat, Slc18a3, Slc5a7, Scn1b, Crybb2, Tsga10ip, and Vstm21) involved in intraocular pressure elevation. Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

2024-04-01·Diabetes

KD025 Is a Casein Kinase 2 Inhibitor That Protects Against Glucolipotoxicity in β-Cells

Article

作者: Vetere, Amedeo ; Small, Jonnell C. ; Glass, Michael A. ; Carbone, Kaycee ; Devkota, Ranjan ; Wagner, Bridget K.

Glucolipotoxicity (GLT), in which elevated levels of glucose and fatty acids have deleterious effects on β-cell biology, is thought to be one of the major contributors in progression of type 2 diabetes. In search of novel small molecules that protect β-cells against GLT, we previously discovered KD025, an inhibitor of Rho-associated coiled-coil–containing kinase isoform 2 (ROCK2), as a GLT-protective compound in INS-1E cells and dissociated human islets. To further understand the mechanism of action of KD025, we found that pharmacological and genetic inhibition of ROCK2 was not responsible for the protective effects of KD025 against GLT. Instead, kinase profiling revealed that KD025 potently inhibits catalytic subunits of casein kinase 2 (CK2), a constitutively active serine/threonine kinase. We experimentally verified that the inhibition of one of the catalytic subunits of casein kinase 2, CK2A1, but not CK2A2, improved cell viability when challenged with GLT. We conclude that KD025 inhibits CK2 to protect β-cells from GLT.Article Highlights

2024-02-01·British Journal of Pharmacology

Transcriptome‐level discovery of survival‐associated biomarkers and therapy targets in non‐small‐cell lung cancer

Article

作者: Győrffy, Balázs

AbstractBackground and PurposeSurvival rate of patients with lung cancer has increased by over 60% in the recent two decades. With longer survival, the identification of genes associated with survival has emerged as an issue of utmost importance to uncover the most promising biomarkers and therapeutic targets.Experimental ApproachAn integrated database was set up by combining multiple independent datasets with clinical data and transcriptome‐level gene expression measurements. Univariate and multivariate survival analyses were performed to identify genes with higher expression levels linked to shorter survival. The strongest genes were filtered to include only those with known druggability.Key ResultsThe entire database includes 2852 tumour specimens from 17 independent cohorts. Of these, 2227 have overall survival data and 1256 samples have progression‐free survival time. The most significant genes associated with survival were MIF, UBC and B2M in lung adenocarcinoma and ANXA2, CSNK2A2 and KRT18 in squamous cell carcinoma. We also aimed to reveal the best druggable targets in non‐smokers lung cancer. The three most promising hits in this cohort were MDK, THY1 and PADI2. The established lung cancer cohort was added to the Kaplan–Meier plotter (https://www.kmplot.com) enabling the validation of future gene expression‐based biomarkers in both the present and yet unexamined subgroups of patients.Conclusions and ImplicationsIn this study, we established a comprehensive database of transcriptome‐level data for lung cancer. The database can be utilized to identify and rank the most promising biomarkers and therapeutic targets for different subtypes of lung cancer.

项与 CSNK2A2 相关的新闻（医药）

2022-03-28

·新浪医药新闻

对奥密克戎变异株无效 FDA修订GSK/VIR新冠抗体疗法EUA说明书

3月25日，葛兰素史克与合作伙伴VIR Biotechnology联合宣布，美国FDA已修订了单抗药物sotrovimab的紧急使用授权（EUA）情况说明书（Fact Sheet）。FDA已经确定，基于所有可用证据，包括VIR产生的新的活病毒数据，sotrovimab 500mg剂量不太可能对奥密克戎BA.2（Omicron BA.2）变异株有效。对此，葛兰素史克与VIR正在准备一套数据以支持更高剂量sotrovimab用于奥密克戎BA.2变异株，并将与世界各地的监管和医疗机构分享这些数据以供讨论。目前，美国FDA已更新了网站信息：根据现有信息，包括变异株对抗体药物的敏感性和区域变异株频率（HHS区域1和2），在可能由非敏感SARS-CoV-2变异株引起感染的地理区域排除使用sotrovimab。FDA将继续监测流行变异株的流行情况，并跟进更新其网站。 sotrovimab是一种SARS-CoV-2中和单克隆抗体，能够与SARS-CoV-2和SARS-CoV-1（引起SARS的病毒）共有的一个表位结合，该表位具有高度保守性，这可能使抗药性的产生更加困难。据了解，sotrovimab融入了Xencor公司的Xtend技术，也被设计用于在肺部实现高浓度，以确保对SARS-CoV-2影响的气道组织实现最佳穿透，并具有延长的半衰期。值得关注的是，2021年5月，FDA授予sotrovimab EUA：作为一种单剂量静脉输注（IV，500mg）疗法，用于直接SARS-CoV-2病毒检测法结果呈阳性、有高风险发展为严重COVID-19（包括住院或死亡）的成人和儿科（年龄≥12岁、体重≥40kg）患者，治疗轻度至中度COVID-19。就在今年1月，葛兰素史克与VIR还向FDA提交了一份申请，对EUA进行修订，sotrovimab纳入肌肉注射（IM）给药途径。参考来源：US Food and Drug Administration Revises Emergency Use Authorization for Sotrovimab Due to Omicron BA.2 Subvariant 内容来源于网络，如有侵权，请联系删除，谢谢。

抗体紧急使用授权合作

2022-02-11

·生物谷

吉利德抗病毒药物Veklury(瑞德西韦)：对奥密克戎变异株保持抗病毒活性!

2022年02月11日讯 --吉利德科学（Gilead Sciences）近日发布数据，显示抗病毒药物Veklury（remdesivir，瑞德西韦）对包括奥密克戎（Omicron）在内的10种新型冠状病毒（SARS-CoV-2）变异株具有体外活性。吉利德研究的结果与其他国家（包括比利时、捷克共和国、德国、波兰、美国）的研究人员独立开展的其他体外研究一致，这些研究证实了Veklury对先前发现的多种SARS-CoV-2变异株具有抗病毒活性，包括阿尔法（Alpha，α）、贝塔（Beta，β），伽马（Gamma，γ）、德尔塔（Delta，δ）、奥密克戎（Omicron，o）。该研究通过2种方法分析了体外抗病毒活性，以了解10种主要SARS-CoV-2变异株对Veklury的易感性。研究结果显示，Veklury对这些变异株以及在西雅图发现的早期祖先A谱系分离株（WA1株）具有类似的活性。具体而言，Delta和Omicron变异株仍然对Veklury完全敏感，这些实验室结果表明，Veklury对过去2年中分离的所有主要变异株都保持活性。这项研究的结果已提交至同行评议期刊以供发表，并已作为预印本上传到BioRxiv。详见：Remdesivir and GS-441524 retain antiviral activity against Delta, Omicron, and other emergent SARS-CoV-2 variants | bioRxiv。 Veklury（瑞德西韦）是吉利德科学公司的一款抗病毒药物，可以阻止新型冠状病毒（SARS-CoV-2）的复制，这种病毒可引起新型冠状病毒肺炎（COVID-19）。Veklury一种核苷酸类似物的前体药物，通过靶向病毒RNA聚合酶直接抑制宿主细胞内的SARS-CoV-2病毒复制。进入人体后，Veklury被转化为活性代谢物瑞德西韦三磷酸，然后结合到病毒RNA中，阻断病毒在所感染细胞内的复制。该研究分析了近600万个公开可用的变异分离株序列，并证实了nsp12蛋白（Veklury的RNA聚合酶靶点）在所有变异株中高度保守。进一步的鉴定证实，在一些SARS-CoV-2变异株中流行的为数不多的nsp12突变均不会影响病毒对Veklury的易感性。吉利德科学病毒学研究高级副总裁Tomas Cihlar表示：“这些结果提供了Veklury对整个大流行期间出现的各种已知变异株（包括奥密克戎）具有持续和持久抗病毒活性的证据，支持其继续用于治疗当前的SARS CoV-2变异株。现在，随着一种新版本的Omicron（BA.2亚变异株）在世界各地的流行，这些最新数据也表明Veklury将保留针对这种新的亚变异株的抗病毒活性，因为Veklury所靶向的病毒RNA聚合酶不包含任何额外的独特突变。吉利德将持续评估Veklury对病毒变异株的活性。” 原文出处：Veklury® (Remdesivir) Retains Antiviral Activity Against Omicron, Delta and Other Emergent SARS-CoV-2 Variants in Multiple In Vitro Studies 内容来源于网络，如有侵权，请联系删除，谢谢。

2022-02-11

·生物谷

对奥密克戎变异株有完全中和活性！礼来与美国政府签订7.2亿美元协议：供应60万剂单抗bebtelovimab!

2022年02月11日讯--礼来（Eli Lilly）近日宣布与美国政府达成协议，以至少7.2亿美元的价格供应多达60万剂的研究性单抗药物bebtelovimab。如果被美国FDA授予紧急使用授权（EUA），美国政府将接受这60万剂的bebtelovimab。礼来已向美国FDA提交了bebtelovimab EUA申请：用于某些高危患者，治疗轻度至中度COVID-19。假病毒和真病毒测试表明，bebtelovimab对奥密克戎（Omicron）变异株保持完全中和活性，这是目前美国的主要变异株。此外，假病毒测试表明，bebtelovimab对所有其他受关注的已知变异株（包括BA.2变异株）保持中和活性。该供应协议要求在2022年3月31日之前交付多达60万剂，并可选择在2022年7月31日之前额外交付50万剂。在2022年，该供应协议的预计财务影响为至少7.2亿美元的收入和大约0.20美元的每股收益。 bebtelovimab（LY-COV1404；LY38 531）是一种针对SARS COV-2棘蛋白的中和IgG1单克隆抗体（mAb），维持了针对目前已知和报道的所有变异株的结合和中和活性，包括奥密克戎（Omicron）和BA.2。目前，bebtelovimab正被研究作为单一疗法以及与其他单抗合用，治疗轻度至中度COVID-19。bebtelovimab由AbCellera和美国国家过敏和传染病研究所（NIAID）疫苗研究中心的科学家发现，礼来已获得授权并开发bebtelovimab。礼来充分利用其专业知识，开发了第一种获美国FDA授予紧急使用授权（EUA）的单抗——bamlanivimab，随后是bamlanivimab与etesevimab组合疗法的EUA。虽然bamlanivimab与etesevimab组合疗法目前未被授权在美国使用，但FDA将参考现有信息，包括关于变体敏感性的信息，以及CDC区域变体频率数据，监测情况以确定在某个区域的使用是否在医学上适合。迄今为止，美国已有超过70万名患者接受了礼来的单抗治疗，在疫情最严重的时期，这可能会阻止超过3.5万人住院，至少1.4万人死亡。原文出处：Lilly will supply up to 600,000 doses of bebtelovimab to U.S. government in ongoing effort to provide COVID-19 treatment options 内容来源于网络，如有侵权，请联系删除，谢谢。