The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid tumors. An investigational drug is one that has not been approved by the U.S. Food & Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.
The goals of this part of the study are:
* Establish a recommended dose of silmitasertib in combination with chemotherapy
* Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer
* To determine the activity of study treatments chosen based on:
* How each subject responds to the study treatment
* How long a subject lives without their disease returning/progressing

开始日期2024-11-30

申办/合作机构

Hershey Medical Center

NCT06202521 / Recruiting临床2期

Evaluation of the Safety and Efficacy of Silmitasertib (CX-4945) in Combination with Standard of Care (SOC) for Treating Patients with Community-Acquired Pneumonia (CAP) Associated with SARS-CoV-2 and Influenza Viral Infections

This is a Phase II, multi-center, double-blind, randomized, interventional study in approximately 120 subjects to evaluate clinical benefit of CX-4945 in adult outpatients with SARS-CoV-2 and influenza viral infection-associated pneumonia. The subjects will be recruited into two domains, including SARS-CoV-2 and influenza virus domains. The study will compare the efficacy of Standard of Care (SOC) combined with CX-4945 against SOC paired with a placebo, utilizing a 1:1 allocation ratio in each domain.

开始日期2024-02-27

申办/合作机构

生华生物科技股份有限公司

NCT05817708 / Completed临床1期

A Dose Selection Phase 1 Study Evaluating the Safety and Tolerability of Silmitasertib

This is a Phase I single center, open-label, parallel design in 30 subjects to evaluate safety and tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each regimen) for continuously 5 days in healthy subjects for dose selection.

开始日期2022-11-07

申办/合作机构

生华生物科技股份有限公司

100 项与 CK2 相关的临床结果

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100 项与 CK2 相关的转化医学

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0 项与 CK2 相关的专利（医药）

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5,736

项与 CK2 相关的文献（医药）

2024-12-01·Journal of Trace Elements in Medicine and Biology

Distinctive expression and cellular localisation of zinc homeostasis-related proteins in breast and prostate cancer cells

Article

作者: Nesarajah, Abinaya N ; Zaman, Mohammad S ; Barman, Shital K ; Wu, Ming J ; Malladi, Chandra S ; Mahns, David A

BACKGROUNDZinc transport proteins (ZIP and ZnT), metallothioneins (MT) and protein kinase CK2 are involved in dysregulation of zinc homeostasis in breast and prostate cancer cells. Following up our previous research, we targeted ZIP12, ZnT1, MT2A and CK2 in this study by investigating their expression levels and protein localisation.METHODSQuantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence confocal microscopy were employed to quantify the expression of ZIP12, ZnT1, MT2A and CK2 subunits in a panel of breast and prostate cell lines without or with extracellular zinc exposure. The cellular localisations of these target proteins were also examined by immunofluorescence confocal microscopy.RESULTSIn response to the extracellular zinc exposure, the gene expression was elevated for SLC39A12 (ZIP12), SLC30A1 (ZnT1) and MT2A (MT2A) in normal prostate epithelial cells (RWPE-1) in contrast to their cancerous counterparts (PC3 and DU145), whilst the gene expression was higher for SLC39A12 (ZIP12) and SLC30A1 (ZnT1) in both normal (MCF10A) and basal breast cancer cells (MDA-MB-231) compared to luminal breast cancer cells (MCF-7). At the protein level, the expression for both ZIP12 and ZnT1 was trending lower in the time course for the breast cancer cells whilst their expression was remained constant in the normal breast epithelial cells. The expression of ZIP12 in prostate cancer cells was higher than the normal prostate cells. The protein expression for CK2 α/αꞌ and CK2β was markedly higher in prostate cancer cells than the normal prostate cells. Upon extracellular zinc exposure, ZIP12 was, for the first time, conspicuously localised in the plasma membrane of breast cancer cells but not in normal breast epithelial cells and prostate cells. ZnT1 is only localised in the plasma membrane of breast cancer cells. MT2A is distinctively seen close to the plasma membrane in breast cancer cells. CK2 is also for the first time shown to be localised in proximity to the plasma membrane of breast cancer cells.CONCLUSIONThe findings, particularly the localisation of ZIP12 and CK2, are novel and significant for our understanding of zinc homeostasis in breast and prostate cancer cells.

2024-12-01·Clinical Proteomics

Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients

Article

作者: Van Nynatten, Logan Robert ; Kaneko, Tomonori ; Abdo, Rober ; Zhong, Shanshan ; Slessarev, Marat ; Fraser, Douglas D ; Ye, Mingliang ; Li, Shawn Shun-Cheng ; Ezra, Sally ; Hovey, Owen ; Voss, Courtney ; Liu, Xuguang

AbstractSARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.

2024-11-01·International Journal of Biological Macromolecules

A comprehensive review on the dynamics of protein kinase CK2 in cancer development and optimizing therapeutic strategies

Review

作者: Du, Yi ; Cui, Hongjuan ; Ghani, Muhammad Usman ; Yi, Du ; Shi, Junbo ; Zhong, Liping

Protein kinase 2 (CK2) is an enzyme ubiquitously present and exhibits extensive kinase activity. It has been strongly linked to tumor progression through the abnormal phosphorylation of key proteins. Research has consistently demonstrated that CK2 is deregulated in various cancer types, with enhanced protein expression and nuclear distribution in tumor cells. CK2 plays a crucial role in a complex network that promotes cell infiltration, migration, proliferation, apoptosis, and cancer progression through multiple pathways, including PI3K/AKT, JAK2/STAT3, ATF4/CDKN1, and HSP90/Cdc37. In addition to its role in cancer growth, there is mounting evidence that CK2 may also affect the immunological dynamics of cancer by altering immune cell functions within the tumor microenvironment, thus facilitating tumor immune evasion. Recent research has increasingly focused on CK2, recognizing it as a therapeutic objective for oncological interventions. This review will critically examine the structure and signaling pathways of CK2, highlighting the significance of further research aimed at enhancing our understanding of the CK2 machinery. Finally, we conclude by refining therapeutic options, notably transitioning from non-pharmacological techniques to strategic CK2 inhibitor use. This development shortens the path to the desired outcome, establishing a pioneering standard in cancer therapy.

项与 CK2 相关的新闻（医药）

2024-09-13

·PRNewswire

US FDA Grants RPD Designation to Senhwa Biosciences Silmitasertib for Pediatric Neuroblastoma

TAIPEI and SAN DIEGO, Sept. 13, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that its new drug Silmitasertib (CX-4945) was granted a rare pediatric disease designation (RPDD) by US FDA for the treatment of neuroblastoma. This is the recognition obtained again after Silmitasertib (CX-4945) received RPDD in medulloblastoma from the FDA in July 2020, demonstrating the great potential of Silmitasertib (CX-4945) in the development of treatments for rare pediatric cancers. Silmitasertib is a first-in-class small molecule drug that targets the CK2 protein and acts as a CK2 inhibitor that exhibited antitumor activity in pre-clinical study of neuroblastoma. The RPD designation will qualify the drug for the priority review voucher (PRV) program meant to encourage development of novel therapies for rare pediatric diseases. Silmitasetib has previously granted 1 RPD and 3 orphan drug designations (ODD) by the FDA. "The RPD designation offers sponsors the additional incentive by requesting priority review vouchers (PRVs) for their future marketing applications, and this approach encourages the drug development for the treatment of rare pediatric diseases," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. Neuroblastoma, an embryonic tumor of the peripheral sympathetic nervous system, is the third most common pediatric cancer and the most common cancer in infants. It is mostly diagnosed in infancy at an average of 1 to 2 years old. There are an estimated 700 to 800 new cases of neuroblastoma each year in the United States. While low and intermediate-risk neuroblastoma have a very high rate of survival, high-risk neuroblastoma has a 5-year survival rate of about 50%, and it has a high likelihood of recurrence even with intense multimodal treatments. There is currently no standard treatment for patients with relapsed/refractory neuroblastoma. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

孤儿药优先审批突破性疗法

2024-08-31

·生物谷

解锁帕金森病的新治疗靶点！Nat Commun｜蛋白质基因组网络分析揭示帕金森病的失调机制和潜在的介质

帕金森病（PD）是一种影响中枢神经系统的退行性疾病，在美国大约有100万人受到它的影响，而预计到2042年，全球的患者人数可能会攀升至1290万。作为仅次于阿尔茨海默病的第二大神经退行性疾病，帕金森病主要影响老年人群，在85至89岁年龄段达到发病高峰，并且男性比女性更容易患病。在临床上，帕金森病患者会经历多种运动和非运动症状，这些症状给他们的日常生活带来了诸多不便。病理特征上，帕金森病表现为黑质区域神经元的丧失，导致纹状体内的多巴胺含量减少，并伴有中脑区域出现的路易小体。虽然高龄被认为是帕金森病的主要风险因素之一，但生活方式的选择，如饮食习惯，以及环境暴露也同样在疾病的发展过程中扮演了重要角色。在过去十年里，遗传学研究揭示了一些与家族性帕金森病相关的罕见基因突变，并通过大规模全基因组关联研究GWAS）发现了散发性帕金森病的多基因背景。尽管已知的遗传变异解释了大约22%的遗传易感性，但至今为止确认的遗传位点只能解释其中的一小部分。为了填补这一空白，需要更多的病例研究。此外，理解帕金森病风险变异的功能影响对于确定潜在的治疗目标至关重要。然而，尽管人类遗传学在药物研发中用于识别和验证靶标，但GWAS信号往往不能明确指出致病基因。蛋白质组学研究可以补充这一不足，因为它能帮助我们了解帕金森病风险变异的功能效应，并可能识别出治疗目标和潜在生物标志物。蛋白质不仅是细胞结构的基础，也是许多调节过程的关键参与者，它们的作用不仅取决于其数量，还包括其相互作用、运输以及翻译后的修饰。因此，蛋白质组学研究具有巨大的潜力，可以作为生物标志物、治疗目标及疾病进程监测的工具。近期的技术进步使得大规模的人群蛋白质组学研究成为可能，例如英国生物银行制药蛋白质组学项目（UKB-PPP），就为研究基因-蛋白质相互作用提供了新的机会。图片来源：https://doi.org/10.1038/s41467-024-50718-x 近日，来自美国的研究者们在Nat Commun杂志上发表了题为“Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson's disease”的文章，这项研究通过蛋白质基因组网络分析揭示了帕金森病中的失调机制和潜在的介质，有助于我们更好地理解帕金森病中的基因-蛋白质动态，并为识别与GWAS信号相关的潜在介质提供了范例。蛋白质基因组网络分析图片来源：https://doi.org/10.1038/s41467-024-50718-x 在这项研究中，研究者开发了一个三相系统级蛋白质基因组学分析框架来表征疾病相关蛋白质和失调机制。蛋白质基因组学分析确定了577种丰富帕金森病相关途径的蛋白质，如细胞因子受体相互作用和溶酶体功能，以及9种在疾病发病机制中具有潜在作用的蛋白，包括LGALS3、CSNK2A1、SMPD3、STX4、APOA2、PAFAH1B3、LDLR、HSPB1、BRK1。蛋白质基因组网络分析揭示了帕金森病的失调机制和潜在的介质示意图图片来源：https://doi.org/10.1038/s41467-024-50718-x 综上所述，通过整合UkB蛋白质基因组数据，研究者们创建了一个网络模型，以描绘基因组-蛋白质组的关系及其相互作用。这种综合方法为理解帕金森病及其他复杂疾病的遗传驱动蛋白破坏提供了一个全面的视角，并为进一步研究这些受影响的蛋白质奠定了基础。参考文献： Abolfazl Doostparast Torshizi et al. Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson's disease. Nat Commun. 2024 Jul 31;15(1):6430. doi: 10.1038/s41467-024-50718-x. 本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~

2024-08-28

·PRNewswire

Unravel Biosciences and CSNK2A1 Foundation Announce Expansion of Collaboration to Identify Drug Candidates for Okur-Chung Neurodevelopmental Syndrome

New study will use Unravel's AI platform to stratify patients into subgroups based on their likelihood to respond to prioritized drugs identified in earlier phase of research. BOSTON, Aug. 28, 2024 /PRNewswire/ -- Unravel Biosciences, Inc., ("Unravel"), an AI-enabled therapeutics company established to advance drugs for complex diseases, and the CSNK2A1 Foundation ("Foundation") today announced that they are expanding their drug discovery collaboration to now stratify Okur-Chung Neurodevelopmental Syndrome (OCNDS) patients into subgroups based on their predicted response to selected drugs. Through a previously announced collaboration, Unravel's proprietary BioNAV™ drug discovery platform used RNA data from patient-derived cells and mouse models to identify in silico drug hits. The Unravel study revealed that patient response to predicted drugs may vary significantly based on the location of their specific CSNK2A1 gene mutation causing OCNDS. The Foundation independently confirmed several in silico hits in a Drosophila fruit fly animal model of OCNDS that have the potential for clinical benefit through a screen with Dr. Clement Chow at the University of Utah. As part of its rareSHIFT™ discovery services, Unravel will utilize its proprietary nasal swab collection methodology in the new project to collect RNA transcriptomes from OCNDS patients and matched healthy family members. The data will be processed using BioNAV™ to identify drug candidates most likely to work for patients with specific genetic mutations. This project focuses on the most prevalent OCNDS-causing mutation, K198R, located in the activation segment of CSNK2A1. Currently the Foundation has over 70 individuals registered with this specific variant. "Given that even monogenetic disorders have substantial variability in how they clinically present and respond to drugs, having a data-driven preview of drug response in real patients is essential to clinically derisk preclinical programs like this," said Richard Novak, Ph.D., Unravel Co-Founder and CEO. "By matching each patient to a drug candidate, we will increase the probability of success in clinical trials and reduce the time and cost of developing meaningful therapies for OCNDS patients." "This innovative approach allows us to move beyond a one-size-fits-all model, offering the possibility of more personalized and effective therapies for our community," explained Gabrielle Rushing, Ph.D., CSNK2A1 Foundation Science Program Director. "The insights gained from stratifying patients by their specific genetic mutations will be invaluable in our ongoing mission to accelerate the development of meaningful treatments for OCNDS." First described in 2016, OCNDS is an ultra-rare genetic syndrome caused by a mutation on chromosome 20 in the CSNK2A1 gene. OCNDS affects every aspect of life, with symptoms ranging from mild to severe and can include the inability to speak or delayed speech, global developmental delay, epilepsy, autism spectrum disorder traits, behavioral challenges, hypotonia, feeding difficulty, and severe sleep disruption. To date, there is no treatment for OCNDS. While the overall prevalence of OCNDS is not fully known, over 250 individuals worldwide are currently registered with the Foundation. About Unravel Biosciences Unravel Biosciences is the first rapid prototyping therapeutics company, integrating AI systems biology computation with rapid in vivo screening and clinical validation of discovered targets with unprecedented efficiency. Unravel leverages its proprietary BioNAV™ platform combining target and drug discovery, preclinical screening and patient stratification to find treatments for complex diseases. Unravel's platform has led to four clinical trials starting in 2024. Unravel's platform developed RVL002, a first-in-class new small molecule targeting mitochondrial metabolism, and RVL027, a molecule targeting a novel mechanism to treat dystonias. The rareSHIFT™ program provides platform access to foundation and biotech partners to accelerate and clinically derisk therapeutics. and About CSNK2A1 Foundation CSNK2A1 Foundation is focused on finding a cure for Okur-Chung Neurodevelopmental Syndrome and ensuring affected individuals have the opportunities and supports necessary for happy and full lives. CSNK2A1 Foundation is a 501(c)(3) non-profit organization that is operated and funded by a committed team of volunteers, advocates, and researchers. To date, the foundation has registered over 250 individuals with OCNDS in its patient registry worldwide. SOURCE Unravel Biosciences, Inc.

临床研究