Molecular Basket Trial In Multiple Malignancies With Common Target Pathway Aberrancies: A Phase II Trial of GSK2256098 and Trametinib in Patients With Advanced Pancreatic Cancer

This is a phase 2 study (the second phase in testing a new drug or combination to see how effect the drug or combination is) of investigational drugs GSK2256098 and Trametinib.
The purpose of the study is to evaluate the antitumor activity of GSK2256098 and Trametinib in patients with advanced pancreatic cancer.

开始日期2016-04-01

申办/合作机构

University Health Network

[+1]

NCT02551653

/ Completed临床1期

A Microdose Study to Evaluate the Biodistribution of [11C]-GSK2256098 in the Lungs and Heart of Healthy Subjects and Idiopathic Pulmonary Arterial Hypertension (PAH) Patients Using Positron Emission Tomography (PET)

Pulmonary arterial hypertension (PAH) involves the narrowing of blood vessels connected to and within the lungs. Focal adhesion kinase (FAK) is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes which leads to stiffening and thickening of blood vessels in lungs. This further increases the blood pressure within the lungs and impairs their blood flow. This study aims to demonstrate biodistribution of FAK inhibitor, GSK2256098, in cardiopulmonary sites i.e. heart and lung tissues. The uptake of 11C-radiolabelled GSK2256098 within the lung and / or heart of healthy subjects and idiopathic pulmonary arterial hypertension (iPAH) patients will be assessed using Positron Emission Tomography (PET). Based on study results the decision as to whether a follow-on phase 2 trial should be initiated to investigate the therapeutic utility of GSK2256098 in iPAH will be decided. Sufficient number of subjects will be screened (up to 30 days prior to scan) to enrol 12 healthy subjects and 12 PAH patients in the study. Enrolled subjects will receive a microdose of [11C]-GSK2256098 on a scanning day which will be followed by the follow-up visit (2-4 weeks post-last dose).

开始日期2015-11-17

申办/合作机构

GSK Plc

NCT02523014

/ Recruiting临床2期IIT

Phase II Trial of SMO/ AKT/ NF2/CDK Inhibitors in Progressive Meningiomas With SMO/ AKT/ NF2/CDK Pathway Mutations

This phase II trial studies how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

开始日期2015-09-28

申办/合作机构

Alliance Foundation Trials LLC

[+4]

100 项与 GSK-2256098 相关的临床结果

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100 项与 GSK-2256098 相关的转化医学

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100 项与 GSK-2256098 相关的专利（医药）

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项与 GSK-2256098 相关的文献（医药）

2025-06-01·BIOORGANIC CHEMISTRY

Discovery and characterization of novel FAK inhibitors for breast cancer therapy via hybrid virtual screening, biological evaluation and molecular dynamics simulations

Article

作者: Pan, Youlu ; Huang, Wenhai ; Chen, Runmei ; Li, Qin ; Deng, Yaru ; Yang, Xinle ; Xu, Xiangwei ; Chi, Xinglong ; Chen, Roufen ; Zhou, Peng ; Pan, Zhichao ; Xu, Yingxuan

Focal adhesion kinase (FAK) is a critical drug target implicated in various disease pathways, including hematological malignancies and breast cancer. Therefore, identifying FAK inhibitors with novel scaffolds could offer new opportunities for developing effective therapeutic compounds. Herein, we disclosed the discovery of a new backbone inhibitor of FAK using an "internal" database, employing a structure-based high-transparency permeability virtual screening (HTVS) and a DeepDock algorithm based on geometric deep learning. Subsequently, molecular docking was conducted at different precisions to identify 10 compounds for further evaluation of biological activity. Ultimately, compound 4, a pyrimidin-4-amine derivative, demonstrated inhibitory activity against FAK and breast cancer cells, further supporting its potential as a FAK inhibitor. Moreover, molecular dynamics simulations were carried out to gain more detailed insights into the binding mechanism between compound 4 and FAK to guide subsequent structural optimization.

2025-03-01·Journal of Computational Biophysics and Chemistry

A Computational Perspective into Binding Mechanism of a potent FAK Inhibitor as Anticancer Drug Candidate: Insights from Molecular Dynamics Simulations

作者: Shogi, F. ; Gholamin, D. ; Razzaghi-Asl, N.

Focal adhesion kinase (FAK) is an important non-receptor tyrosine kinase (nRTK) with crucial role in primary cell functions. Fundamental cellular processes, such as migration, adhesion, proliferation, and survival, are regulated by FAK. The tumorigenesis of FAK is very important since it is overexpressed in advanced cancers, causes malignant features and induces cancer metastasis. The available evidence proposes FAK as a promising target for cancer therapy. At the moment, there are no FAK inhibitors (FAKIs) in the market but several small molecule FAKIs have been developed and a few of them entered into clinical studies as anticancer agents. In spite of these achievements, development of selective and potent FAKIs may be partly hampered by the lack of crystallographic or structural data. This limitation could be resolved through proposing robust ligand–protein binding models to design new FAKIs. GSK2256098 is a small molecule ATP-competitive FAKI that undergoes clinical trials as a monotherapy or in combination with other medications against advanced solid tumors. GSK2256098 have been proven to be a selective and potent agent (IC[Formula: see text] 0.4 nM) with respect to other clinical candidates. With regard to appropriate characteristics, this molecule is particularly amenable for performing computational modeling studies. In this study, we try to propose an applicable binding model of GSK2256098 inside the FAK kinase domain. For this purpose, molecular docking, all-atom 200-ns molecular dynamics simulations and free-energy-calculation methods were applied as consecutive modeling techniques. Atomic insight and dynamic evolution of the system were used to attain a stable binding mode and infer chemical interactions of GSK2256098 inside the kinase domain of FAK. Although complementary investigations need to be conducted, obtained results may offer a structural basis for the development of potent and selective FAKIs.

2024-12-01·BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Modeling of FAK-PROTAC candidates from GSK2256098 analogs for targeted protein degradation

Article

作者: Lee, Keun Woo ; Parate, Shraddha ; Jung, Tae Sung ; Kumar, Vikas ; Ro, Hyeon-Su

Protein inhibition via the traditional drug-designing approach has been shown to be an effective method for developing numerous small-molecule-based therapeutics. In the last decade, small inhibitors-guided protein degradation has arisen as an alternative method with the potential to fulfill the drug requirement for undruggable targets. Focal adhesion kinase (FAK) is a crucial modulator of the growth and spread of tumors, apart from it also acts as a scaffold for signaling of other proteins. FAK inhibitors have thus far had unsatisfactory results in clinical trials for cancer applications. Unlike prior attempts to control FAK expression, which were restricted to kinase domain inhibition with limited success in clinical research, protein degradation has the potential to concurrently disrupt FAK's kinase and scaffolding function. Recently, several FAK degraders were reported based on FAK Type I inhibitors using complex chemical synthesis approaches. Interestingly, recently a ternary complex was published revealing the binding mode of the FAK-PROTAC-E3 complex. This complex opens an avenue for the development of rational PROTAC design against FAK protein. Therefore, in the present study, we selected the most active Type I FAK inhibitor GSK2256098. The binding mode of the inhibitor prompted us to identify the most suitable analog for PROTAC design. We have identified a high-affinity analog that is suitable for PTOTAC design through the application of molecular docking (MD) and molecular dynamics simulations (MDS). Further based on the ternary FAK-PROTAC-E3 complex we build a binary complex FAK-Hit-E3-VHL between both proteins. Using the structure-based approach ten different potential FAK PROTACs candidates were designed. The stability of the complexes was analyzed using MDS and binding free energies were used to predict the binding affinity. Finally, based on desirable intermolecular interactions with the target and E3 ligase ProTAC4 was selected as the best candidate when compared with known FAK PROTAC GSK215.

项与 GSK-2256098 相关的新闻（医药）

2023-05-08

·PRNewswire

Global Pancreatic Cancer Competitive Landscape Report 2023: Comprehensive Insights about 250+ Companies and 300+ Drugs

DUBLIN, May 8, 2023 /PRNewswire/ -- The "Pancreatic Cancer - Competitive landscape, 2023" report has been added to ResearchAndMarkets.com's offering. This "Pancreatic Cancer- Competitive landscape, 2023" report provides comprehensive insights about 250+ companies and 300+ drugs in Pancreatic Cancer Competitive landscape. It covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. In March 2023, Adaptimmune Therapeutics plc. and TCR Therapeutics Inc. (NASDAQ: TCRR), announced entry into a definitive agreement under which Adaptimmune will combine with TCR in an all-stock transaction to create a preeminent cell therapy company focused on treating solid tumors. The combination provides extensive benefits for clinical development and product delivery supported by complementary technology platforms. As a result, and following the closing of the transaction, it is anticipated that the combined company's cash runway will extend into 2026. In February 2023, Akamis Bio, announced an expansion of its ongoing partnership with the Parker Institute for Cancer Immunotherapy (PICI) to include a clinical collaboration with the Cancer Research Institute (CRI) that will focus on advancing novel treatments for pancreatic cancer. As part of the Akamis Bio, PICI, and CRI partnership, NG-350A, an immuno-stimulatory tumor gene therapy driving intratumoral expression of a CD40 agonist monoclonal antibody, will be evaluated in combination with standard-of-care chemotherapy and the CTLA-4 inhibitor ipilimumab (YERVOY). In February 2023, Gritstone bio, Inc. announced that it has entered into a clinical trial agreement with the National Cancer Institute (NCI), an institute of the National Institutes of Health, to evaluate an autologous T cell therapy expressing a T cell receptor targeting mutated KRAS in combination with Gritstone's KRAS-directed vaccine candidate, SLATE-KRAS, in a Phase 1 study. Under the terms of the agreement, NCI will identify patients with metastatic cancer that are eligible for adoptive cell transfer based on the presence of a G12V or G12D KRAS mutation (KRASmut). In February 2023, Keymed Biosciences Inc., jointly announced a global exclusive license agreement with AstraZeneca for CMG901, a potential first-in-class Claudin 18.2 antibody drug conjugate (ADC). Under the license agreement, AstraZeneca will be responsible for the research, development, manufacture and commercialization of CMG901 globally. CMG901 is currently in a Phase I clinical trial for the treatment of Claudin 18.2-positive solid tumors. In January 2023, AIM ImmunoTech Inc. announced it has entered into an external sponsored collaborative clinical research agreement with Erasmus MC and AstraZeneca. Under the agreement, Erasmus MC is planning to perform an investigator-initiated clinical study, entitled "Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect. DURIPANC Study," in which it will use both Study Drugs provided by AstraZeneca and AIM ImmunoTech. Pancreatic Cancer Analytical Perspective In-depth Commercial Assessment: Pancreatic Cancer Collaboration Analysis by Companies The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form. Key Questions Answered Current Treatment Scenario and Emerging Therapies: How many companies are developing Pancreatic Cancer drugs? How many Pancreatic Cancer drugs are developed by each company? How many emerging drugs are in mid-stage, and late-stage of development for the treatment of Pancreatic Cancer? What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the Pancreatic Cancer therapeutics? What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies? What are the clinical studies going on for Pancreatic Cancer and their status? What are the key designations that have been granted to the emerging and approved drugs? Key Players Panbela Therapeutics ERYtech Pharma Jiangsu HengRui Medicine Co., Ltd. FibroGen Novartis AG AB Science TME Pharma AG Intensity Therapeutics Silenseed LTD SynerGene Therapeutics Elevation oncology Salspera LLC Redx Pharma Plc AIM ImmunoTech Inc. Rain Oncology Jazz Pharmaceuticals Invyte Corporation Immodulon Therapeutics Ltd GSK plc Merck Sharp & Dohme LLC Roche Helsinn Healthcare SA Argenus Inc. Actuate Therapeutics OSE Immunotherapeutics Incyte Corporation Galera Therapeutics CSPC ZhongQi Pharmaceutical Technology Astellas Pharma Global Development, Inc. NanOlogy Theriva Biologics AstraZeneca Berg, LLC Agenus ABVC BioPharma, Inc. Boehringer Ingelheim Alligator Bioscience CARsgenTherapeutics Co.,Ltd Purple Biotech Ltd. Lisata Therapeutics Chongqing Precision Biotech Co., Ltd Cybrexa Therapeutics Bold Therapeutics BioNTech SE Bristol-Myers Squibb DEKA Biosciences Senhwa Biosciences Cue Biopharma Carisma Therapeutics Inc Key Products Olaptesed pegol INT230-6 SBP-101 Masitinib NIS793 siG12D LODER SGT-53 Seribantumab Salmonella-IL2 RXC004 Rintatolimod RAIN-32 Lurbinectedin Retifanlimab IMM-101 GSK2256098 Belzutifan Atezolizumab Anamorelin AGEN1423 Elraglusib OSE2101 Epacadostat GC4711 Docetaxel Zolbetuximab NanoPac VCN-01 Danvatirsen BPM31510 Botensilimab ABV-1703 BI 907828 Mitazalimab CT041 CM24 CEND-1 CEA-targeted CAR-T cells CBX-12 BOLD-100 BNT141 BMS-813160 DK210 CX-5461 CUE-102 CT-0508 For more information about this report visit About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends. Media Contact: Research and Markets Laura Wood, Senior Manager [email protected] For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900 U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716 Logo: SOURCE Research and Markets

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100 项与 GSK-2256098 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16106

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
腺癌	临床2期	加拿大	GSK Plc	2016-04-01
胰腺癌	临床2期	加拿大	GSK Plc	2016-04-01
脑膜瘤	临床2期	美国	GSK Plc	2015-09-28
2型神经纤维瘤病	临床2期	美国	GSK Plc	2015-09-28
特发性肺动脉高压	临床1期	英国	GSK Plc	2015-11-17
晚期恶性实体瘤	临床1期	法国	GSK Plc	2013-11-18
晚期恶性实体瘤	临床1期	英国	GSK Plc	2013-11-18
星形细胞瘤	临床1期	澳大利亚	GSK Plc	2010-07-27
星形细胞瘤	临床1期	法国	GSK Plc	2010-07-27
星形细胞瘤	临床1期	英国	GSK Plc	2010-07-27

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临床结果

适应症

分期

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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


NCT02523014 (Alliance A071401, ASCO2020) 人工标引	临床2期	脑膜瘤 NF2 Mutation	36	GSK-2256098 (Grade I meningiomas)	齋衊構憲衊醖餘糧夢鑰(願築簾製鏇獵齋願鹽蓋) = 艱遞糧積構蓋淵願製衊繭襯鏇構獵範選顧繭選 (淵艱顧遞顧淵網糧鑰膚, 52 ~ 98)	积极	2020-05-25
				GSK-2256098 (Grade II/III meningiomas)	齋衊構憲衊醖餘糧夢鑰(願築簾製鏇獵齋願鹽蓋) = 憲製餘蓋繭鬱築觸選範繭襯鏇構獵範選顧繭選 (淵艱顧遞顧淵網糧鑰膚, 16 ~ 55)
NCT02551653 (CTgov)	临床1期	特发性肺动脉高压	10	GSK2256098 (PAH Participants)	願廠願廠範積夢廠鑰衊(衊蓋壓醖簾廠繭鑰顧鹹) = 齋鹽膚顧鹹獵鹽衊簾選鑰觸獵築襯窪壓艱選網 (選鏇鹹衊憲廠餘鏇製憲, 0.14769) 更多	-	2018-08-17
				GSK2256098 (Healthy Volunteers)	願廠願廠範積夢廠鑰衊(衊蓋壓醖簾廠繭鑰顧鹹) = 餘鹽鹹廠餘鬱簾糧淵範鑰觸獵築襯窪壓艱選網 (選鏇鹹衊憲廠餘鏇製憲, 0.18754) 更多
NCT02428270 (ASCO_GI 12018 \| ASCO_GI 22018) 人工标引	临床2期	晚期胰腺导管腺癌二线	16	trametinib+GSK2256098	構糧憲衊選廠網壓醖鹽(範積繭壓膚窪顧壓淵襯) = 齋壓鹹範鑰糧鏇壓觸觸鑰簾襯鹹蓋觸製鹽憲膚 (鑰襯衊艱築顧廠夢繭艱, 1.5 ~ 1.8) 更多	不佳	2018-01-19
NCT01938443 (ASCO2015) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	24	GSK2256098+trametinib (total population)	觸繭醖鑰鑰醖齋憲壓窪(窪製構願顧範觸繭糧艱) = 醖遞簾夢廠衊壓鹽鑰蓋網築夢觸艱觸獵衊窪廠 (憲鹹構廠壓遞窪窪齋觸 )	积极	2015-05-20
				GSK2256098+trametinib (mesothelioma pts)	艱範構壓膚醖壓蓋構築(顧膚壓簾簾鑰顧選網願) = 夢壓鏇鏇鹽繭顧範構鹹網齋艱夢夢衊繭觸膚鬱 (鑰網淵築齋簾積製衊獵 )
NCT01138033 (ASCO2012)	临床1期	HR阳性/HER2低表达实体瘤	57	GSK2256098	壓觸範廠壓蓋製觸廠鹽(鏇齋淵觸艱衊蓋襯築製) = 襯壓壓鏇窪獵觸壓顧淵艱製膚選願衊餘鬱築糧 (範構積鹹淵憲襯窪壓艱 ) 更多	-	2012-05-20