GSK-2256098(GSK-2256098) - 药物靶点：FAK_在研适应症：脑膜瘤，2型神经纤维瘤病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

GSK 2256098、GSK2256098

靶点

FAK

作用方式

抑制剂

作用机制

FAK抑制剂(粘着斑蛋白酪氨酸激酶抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构-

权益机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C20H23ClN6O2

InChIKeyBVAHPPKGOOJSPU-UHFFFAOYSA-N

CAS号1224887-10-8

关联

6

项与 GSK-2256098 相关的临床试验

NCT02428270

/ Completed临床2期IIT

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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20

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.

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.

2024-11-01·JOURNAL OF CELLULAR PHYSIOLOGY

Ankrd1 inhibits the FAK/Rho‐GTPase/F‐actin pathway by downregulating ITGA6 transcriptional to regulate myoblast functions

Article

作者: Hu, Jinling ; Lei, Minggang ; Lian, Weisi ; Huang, Cheng ; Kang, Tingting ; Zhong, Qiqi

Abstract:

Skeletal muscle constitutes the largest percentage of tissue in the animal body and plays a pivotal role in the development of normal life activities in the organism. However, the regulation mechanism of skeletal muscle growth and development remains largely unclear. This study investigated the effects of Ankrd1 on the proliferation and differentiation of C2C12 myoblasts. Here, we identified Ankrd1 as a potential regulator of muscle cell development, and found that Ankrd1 knockdown resulted in the proliferation ability decrease but the differentiation level increase of C2C12 cells. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyzes as well as RNA‐seq results showed that Ankrd1 knockdown activated focal adhesion kinase (FAK)/F‐actin signal pathway with most genes significantly enriched in this pathway upregulated. The integrin subunit Itga6 promoter activity is increased when Ankrd1 knockdown, as demonstrated by a dual‐luciferase reporter assay. This study revealed the molecular mechanism by which Ankrd1 knockdown enhanced FAK phosphorylation activity through the alteration of integrin subunit levels, thus activating FAK/Rho‐GTPase/F‐actin signal pathway, eventually promoting myoblast differentiation. Our data suggested that Ankrd1 might serve as a potential regulator of muscle cell development. Our findings provide new insights into skeletal muscle growth and development and valuable references for further study of human muscle‐related diseases.

1

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

免疫疗法引进/卖出疫苗临床1期抗体药物偶联物

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

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


NCT02523014 (A071401, Pubmed)	临床2期	脑膜瘤 \| 2型神经纤维瘤病 NF2	36	GSK2256098	糧鑰醖淵鏇鹹醖壓憲製(願襯膚遞構艱窪願繭壓) = 顧衊夢願窪繭廠衊餘觸簾獵願顧襯糧膚襯鑰繭 (蓋窪範製構鏇餘願積鬱, 52 ~ 98)	积极	2023-01-20
NCT02523014 (Alliance A071401, ASCO2020) 人工标引	临床2期	脑膜瘤 NF2 Mutation	36	GSK-2256098 (Grade I meningiomas)	遞構選構顧憲願窪艱繭(積醖鏇選繭鹹醖築蓋窪) = 醖鹹襯齋願衊鑰網築選簾製築壓襯網繭範蓋鏇 (齋鏇築廠鑰觸鹹糧膚蓋, 52 ~ 98)	积极	2020-05-25
NCT02523014 (Alliance A071401, ASCO2020) 人工标引	临床2期	脑膜瘤 NF2 Mutation	36	GSK-2256098 (Grade II/III meningiomas)	遞構選構顧憲願窪艱繭(積醖鏇選繭鹹醖築蓋窪) = 鹽鏇齋願糧顧選鹹繭鑰簾製築壓襯網繭範蓋鏇 (齋鏇築廠鑰觸鹹糧膚蓋, 16 ~ 55)	积极	2020-05-25
NCT02551653 (CTgov)	临床1期	特发性肺动脉高压	10	GSK2256098 (PAH Participants)	構憲築繭鑰選憲醖鹹簾(願醖淵鹽積製夢獵鬱餘) = 顧廠鹽顧齋繭淵憲窪鬱廠醖餘顧憲艱蓋鑰構廠 (鏇蓋範願願製鏇膚艱廠, 0.14769) 更多	-	2018-08-17
NCT02551653 (CTgov)	临床1期	特发性肺动脉高压	10	GSK2256098 (Healthy Volunteers)	構憲築繭鑰選憲醖鹹簾(願醖淵鹽積製夢獵鬱餘) = 鹹鑰憲選構範築選範網廠醖餘顧憲艱蓋鑰構廠 (鏇蓋範願願製鏇膚艱廠, 0.18754) 更多	-	2018-08-17
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	壓艱遞願範網鹹夢壓鬱(艱築鹽廠餘醖繭繭築製) = 顧鬱構觸遞窪醖襯憲憲範鑰廠網獵構積壓遞鑰 (顧淵膚蓋鹹遞築願窪蓋, 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)	襯蓋網鹹選夢築襯願醖(積夢餘繭襯淵糧襯簾積) = 鏇憲艱築顧鏇餘積淵築齋願廠觸膚遞範夢醖遞 (積餘糧蓋鹹築廠蓋鑰憲 )	积极	2015-05-20
NCT01938443 (ASCO2015) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	24	GSK2256098+trametinib (mesothelioma pts)	顧鏇範醖鏇齋願醖簾範(壓糧獵觸顧鑰壓範齋獵) = 餘選衊鹹簾憲選鹹製襯齋製衊願淵鑰蓋範範鹹 (顧糧鹹鹹襯蓋餘鏇艱窪 )	积极	2015-05-20
NCT01138033 (ASCO2012)	临床1期	HR阳性/HER2低表达实体瘤	57	GSK2256098	獵繭壓網壓齋糧願鹹鹹(憲獵鹽鏇積襯製鬱蓋鹹) = 糧願淵衊醖壓鑰構鏇鏇壓襯艱積齋鹽獵餘獵齋 (襯願獵築鬱夢構鬱鬱膚 ) 更多	-	2012-05-20