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2024-10-30

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 Silmitasertib 相关的临床结果

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100 项与 Silmitasertib 相关的转化医学

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100 项与 Silmitasertib 相关的专利（医药）

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228

项与 Silmitasertib 相关的文献（医药）

2025-01-01·METABOLISM-CLINICAL AND EXPERIMENTAL

Body weight control via protein kinase CK2: diet-induced obesity counteracted by pharmacological targeting

Article

作者: Hansen, Daniel ; Guerra, Barbara ; Blagoev, Blagoy ; Doktor, Thomas K. ; Andresen, Brage S. ; Færgeman, Nils J. ; Færgeman, Nils J ; Andresen, Brage S ; Buchwald, Laura M ; Litchfield, David W. ; Neess, Ditte ; Steffensen, Lasse B. ; Ramesh, Vignesh ; Ravnskjaer, Kim ; Doktor, Thomas K ; Buchwald, Laura M. ; Steffensen, Lasse B ; Litchfield, David W

BACKGROUND:

Protein kinase CK2 is a highly conserved enzyme implicated in the pathogenesis of various human illnesses including obesity. Despite compelling evidence for the involvement of this kinase in the pathophysiology of obesity, the molecular mechanisms by which CK2 might regulate fat metabolism are still poorly understood.

METHODS AND RESULTS:

In this study, we aimed to elucidate the role of CK2 on lipid metabolism by employing both in vitro and in vivo approaches using mouse pre-adipocytes and a mouse model of diet-induced obesity. We show that pharmacological inhibition of CK2 by CX-4945 results in premature upregulation of p27^KIP1 preventing the progression of cells into mature adipocytes by arresting their development at the intermediate phase of adipogenic differentiation. Consistent with this, we show that in vivo, CK2 regulates the expression levels and ERK-mediated phosphorylation of C/EBPβ, which is one of the earliest transcription factors responsive to adipogenic stimuli. Furthermore, we demonstrate the functional implication of CK2 in the expression of late markers of adipogenesis and factors regulating lipogenesis in liver and white adipose tissue. Finally, we show that while mice subjected to high-fat diet increased their body weight, those additionally treated with CX-4945 gained considerably less weight. NMR-based body composition analysis revealed that this is linked to significant differences in body fat mass.

CONCLUSIONS:

Taken together, our study provides novel insights into the role of CK2 in fat metabolism in response to chronic lipid overload and confirms CK2 pharmacological targeting as a potentially powerful strategy for body weight control and/or the treatment of obesity and related metabolic disorders.

2025-01-01·MOLECULAR CARCINOGENESIS

Silmitasertib in Combination With Cabozantinib Impairs Liver Cancer Cell Cycle Progression, Induces Apoptosis, and Delays Tumor Growth in a Preclinical Model

Article

作者: Ray, Ratna B. ; Haga, Yuki ; Ray, Ranjit

ABSTRACT:

The rising incidence of hepatocellular carcinoma (HCC) is a global problem. Several approved treatments, including immune therapy and multi‐tyrosine kinase inhibitors, are used for treatment, although the results are not optimum. There is an unmet need to develop highly effective chemotherapies for HCC. Targeting multiple pathways to attack cancer cells is beneficial. Cabozantinib is an orally available bioactive multikinase inhibitor and has a modest effect on HCC treatment. Silmitasertib is an orally bioavailable, potent CK2 inhibitor with a direct role in DNA damage repair and is in clinical trials for other cancers. In this study, we planned to repurpose these existing drugs on HCC treatment. We observed a stronger antiproliferative effect of these two combined drugs on HCC cells generated from different etiologies as compared to the single treatment. Global RNA‐seq analyses revealed a decrease in the expression of G2/M cell cycle transition genes in HCC cells following combination treatment, suggesting G2 phase cell arrest. We observed G2/M cell cycle phase arrest in HCC cells upon combination treatment compared to the single‐treated or vehicle‐treated control cells. The downregulation of CCNA2 and CDC25C following combination therapy further supported the observation. Subsequent analyses demonstrated that combination treatment inhibited 70 kDa ribosomal protein S6 kinase (p70S6K) phosphorylation, and increased Bim expression. Apoptosis of HCC cells were accompanied by increased poly (ADP‐ribose) polymerase cleavage and caspase‐9 activation. Next, we observed that a combination therapy significantly delayed the progression of HCC xenograft growth as compared to vehicle control. Together, our results suggested combining cabozantinib and silmitasertib would be a promising treatment option for HCC.

2025-01-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a novel, selective CK2 inhibitor class with an unusual basic scaffold

Article

作者: Elgaher, Walid A.M. ; Abadi, Ashraf H ; Filhol-Cochet, Odile ; Khalifa, Hend ; Filhol, Odile ; ElHady, Ahmed K. ; Hamed, Mostafa M ; Hamed, Mostafa M. ; Engel, Matthias ; ElHady, Ahmed K ; Cochet, Claude ; Elgaher, Walid A M ; Abdel-Halim, Mohammad ; Abadi, Ashraf H. ; Liu, Ting

CK2 is a Ser/Thr-protein kinase playing a crucial role in promoting cell growth and survival, hence it is considered a promising target for anti-cancer drugs. However, many previously reported CK2 inhibitors lack selectivity. In search of novel scaffolds for selective CK2 inhibition, we identified a dihydropyrido-thieno[2,3-d]pyrimidine derivative displaying submicromolar inhibitory activity against CK2α. This scaffold captured our interest because of the basic secondary amine, a rather unusual motif for CK2 inhibitors. Our optimization strategy comprised the incorporation of a 4-piperazinyl moiety as a linker group and introduction of varying substituents on the pendant phenyl ring. All resulting compounds exhibited potent CK2α inhibition, with IC₅₀ values in the nanomolar range. Compound 10b demonstrated the most balanced activity profile with a cell-free IC₅₀ value of 36.7 nM and a notable cellular activity with a GI₅₀ of 7.3 μM and 7.5 μM against 786-O renal cell carcinoma and U937 lymphoma cells, respectively. 10b displayed excellent selectivity when screened against a challenging kinase selectivity profiling panel. Moreover, 10b inhibited CK2 in the cells, albeit less potently than CX-4945, but induced cell death more strongly than CX-4945. Altogether, we have identified a novel CK2 inhibitory scaffold with drug-like physicochemical properties in a favorable basic pKa range.

项与 Silmitasertib 相关的新闻（医药）

2024-11-07

·Outsourcing Pharma

Senhwa Biosciences starts trial of silmitasertib in children with difficult to treat cancers

Silmitasertib, also known as CX-4945, was originally developed by Cylene Pharmaceuticals, a San Diego-based biotech that ceased operations in 2013. Since then, Senhwa Biosciences, which is headquartered in Taiwan but also has a San Diego base gained the rights to the small molecule, first in class, casein kinase 2 (CK2) inhibitor. CK2 is overexpressed in a number of tumors. Various studies have shown silmitasertib appears to have good anticancer activity. For example , it triggers autophagy and promote apoptosis of cancer cells in pancreatic and lung cancer and also promotes colorectal cancer cell death. Senhwa is currently testing silmitasertib in early human trials for treatment of cholangiocarcinoma, basal cell carcinoma, medulloblastoma and neuroblastoma. In preclinical studies , the small molecule showed good oral bioavailability and was able to effectively inhibit tumor growth in animal studies while being well tolerated. When combined with DNA-damaging chemotherapy drugs such as gemcitabine and cisplatin, the anticancer activity of silmitasertib seems to be enhanced so it is being tested as an add-on therapy in the new trial. The phase 1/2 study will include 114 children and young adults with relapsed or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma in the US. "We are thrilled to be able to move this important research forward on a larger scale," said Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium, which is supporting the study. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally.” Additional indication for Covid-19 patients As well as being a promising anti-cancer therapy, silmitasertib is being tested to treat people infected with SARS-CoV-2 who develop serious symptoms that require hospitalization in a phase 2 study. CK2 is involved in regulating signaling pathways important for innate immune responses. Inhibiting this protein kinase can help reduce the excessive cytokine storm immune response often seen in people with severe Covid-19. Studies have shown that silmitasertib and other kinase inhibitors seem to reduce levels of inflammatory biomarkers such as interleukin 6 and tumor necrosis factor-alpha, both of which are high in hospitalized Covid-19 patients. So far results phase 2 results announced by Senhwa have been good with significantly better recovery times observed for Covid-19 patients given silmitasertib versus standard care, with a good safety profile.

临床2期临床结果临床1期

2024-11-06

·PRNewswire

Senhwa Biosciences announces first patient dosed in the Phase I/II study of Silmitasertib in children and young adults with relapsed refractory solid tumors.

TAIPEI and SAN DIEGO, Nov. 6, 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 the enrollment of the first patient at Penn State Health Children's Hospital in its Phase I/II clinical study evaluating the efficacy of Silmitasertib (CX-4945) in combination with chemotherapy for children and young adults with relapsed or refractory solid tumors. This innovative trial seeks to establish a recommended dose of Silmitasertib in combination with chemotherapy and assess the safety, tolerability and efficacy in patients with cancer, with a focus on neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma. "This clinical trial is a critical piece in understanding the mechanism of how the medicine works and develop more precise treatments for our patients," said Dr. Chandrika Behura, study chair and principal investigator, Four Diamonds researcher and associate professor of pediatrics at the College of Medicine. "It's very important to develop the right combination that can be the most toxic to cancer cells, but the least harmful to the normal cells around them." The study is projected to enroll up to 114 participants nationwide through the Beat Childhood Cancer Research Consortium member hospitals. By evaluating the activity of the study treatments based on individual responses and duration of disease control, the trial aims to develop novel therapeutic approaches. "We are thrilled to be able to move this important research forward on a larger scale," said Dr. Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium. "The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally." With the College of Medicine serving as its home, the Beat Childhood Cancer Research Consortium is a worldwide network of more than 50 universities and children's hospitals focused on saving lives and helping the Children's Hospital make a lasting difference around the world. Funding for this clinical trial is provided by the Beat Childhood Cancer Foundation and the Little Warrior Foundation. Funding for Behura's research which led to the clinical trial was provided by Four Diamonds. "This is the culmination of the work of many people over the years," said Suzanne Graney, executive director of Four Diamonds. "Without the dedication of our physician-scientists and the generosity of our donors and community, this kind of essential work to improve treatments with an ultimate goal of curing cancer would not be possible." The pediatric cancer care specialists at Beat Childhood Cancer Research Consortium hospitals and researchers at the College of Medicine are dedicated to turning groundbreaking discoveries into lifesaving treatments for childhood cancer. "By expanding our research and increasing clinical trials, we are exploring immunotherapy, cellular therapy and precision medicine to deliver the most optimized care to each unique patient," said Dr. Dr. Yatin Vyas, pediatrician-in-chief and chair of the Department of Pediatrics at the Children's Hospital. "We are greatly honored to collaborate with the Penn State College of Medicine and Beat Childhood Cancer Research Consortium, which have been diligently fighting childhood cancers by infusing invaluable resources from over 50 universities and children's hospitals across the United States for the clinical study," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. "We appreciate for having the opportunity of providing Silmitasertib as a potential effective treatment and look forward to realizing its therapeutic value in this urgently needed field for childhood cancers though this study". 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

$Senhwa Biosciences announces first patient dosed in the Phase I/II study of Silmitasertib in children and young adults with relapsed refractory solid tumors.$

临床研究免疫疗法

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

100 项与 Silmitasertib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Silmitasertib	-	DB15408

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
尤文肉瘤	临床2期	美国	生华生物科技股份有限公司	2024-11-06
脂肪肉瘤	临床2期	美国	生华生物科技股份有限公司	2024-11-06
横纹肌肉瘤	临床2期	美国	生华生物科技股份有限公司	2024-11-06
流感病毒感染	临床2期	中国台湾	生华生物科技股份有限公司	2024-02-27
社区获得性肺炎	临床2期	中国台湾	生华生物科技股份有限公司	2024-02-27
新型冠状病毒感染	临床2期	美国	生华生物科技股份有限公司	2020-11-30
胆管癌	临床2期	美国	生华生物科技股份有限公司	-
胆管癌	临床2期	韩国	生华生物科技股份有限公司	-
胆管癌	临床2期	中国台湾	生华生物科技股份有限公司	-
神经母细胞瘤	临床2期	美国	生华生物科技股份有限公司	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02128282 (S4-13-001, Pubmed) 人工标引	临床1/2期	胆管癌一线	84	Gemcitabine+Cisplatin+Silmitasertib	選蓋顧築簾糧廠選鏇艱(鬱範觸餘膚夢襯願遞醖) = 鏇遞夢網鬱遞鏇繭鹽鏇膚顧蓋衊餘膚範醖選遞 (顧繭淵醖蓋選鏇鏇糧憲, 7.6 ~ 14.7) 更多	积极	2022-09-24
NCT02128282 (S4-13-001, Pubmed) 人工标引	临床1/2期	胆管癌一线	84	Gemcitabine+Cisplatin	選蓋顧築簾糧廠選鏇艱(鬱範觸餘膚夢襯願遞醖) = 襯獵選獵衊選製鑰淵鹽膚顧蓋衊餘膚範醖選遞 (顧繭淵醖蓋選鏇鏇糧憲, 3.1 ~ NE) 更多	积极	2022-09-24
NCT02128282 (S4-13-001, ASCO_GI2021) 人工标引	临床1/2期	转移性胆管癌一线	87	gemcitabine+cisplatin+Silmitasertib	窪選製蓋淵衊觸範糧鏇(醖獵鹹鏇積獵構願窪壓) = 製襯衊醖獵餘網鹹鹹構繭鹹膚構糧鏇壓淵積築 (鬱齋積鬱獵獵鹽簾鹹鬱, 7.6 ~ 14.7) 更多	积极	2021-01-22
NCT02128282 (ASCO_GI2017)	临床1/2期	晚期胆道癌	127	CX-4945	觸鹽淵蓋鑰餘壓簾鏇壓(製顧遞憲淵鑰淵遞餘膚) = 顧壓獵鏇憲獵餘簾襯簾積醖醖襯艱衊淵糧壓廠 (醖網簾繭憲範網廠艱製 ) 更多	-	2017-03-21