Tosedostat(Tosedostat) - 在研适应症：膀胱癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Tosedostat (USAN/INN)

靶点-

作用方式

抑制剂

作用机制

氨肽酶家族抑制剂

治疗领域

肿瘤泌尿生殖系统疾病

在研适应症

膀胱癌

非在研适应症

急性淋巴细胞白血病急性髓性白血病晚期恶性实体瘤+ [5]

原研机构

CTI BioPharma Corp.

在研机构

Erasmus University Rotterdam

非在研机构

Chroma Therapeutics Ltd.

University of Cardiff

CTI BioPharma Corp.

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构/序列

分子式C21H30N2O6

InChIKeyFWFGIHPGRQZWIW-SQNIBIBYSA-N

CAS号238750-77-1

关联

16

项与 Tosedostat 相关的临床试验

NCT02352831

/ Terminated临床1/2期IIT

Phase I/II Study Combining Tosedostat With Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma

There are two parts to this study: the goal of the first part of the study is to find the best dose of tosedostat when given in combination with capecitabine. The goal of the second part of the study is to look at how participants respond to treatment with tosedostat and capecitabine.

开始日期2015-08-31

申办/合作机构

Washington University School of Medicine

NCT02452346

/ Completed临床2期IIT

Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Atients With Myelodysplastic Syndromes (MDS) After Failure of Hypomethylating Agent-Based Therapy

Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy.

开始日期2015-03-20

申办/合作机构

Weill Medical College of Cornell University

[+1]

NCT01636609

/ Terminated临床1期IIT

Phase I/II Study of Cytarabine or 5-Azacitidine Combined With Tosedostat to Evaluate the Safety and Tolerability in Older Patients With Acute Myeloid Leukemia (AML) or High Risk MDS

This phase I/II trial studies the side effects and best dose of cytarabine and azacitidine and how well they work when giving together with tosedostat in treating older participants with acute myeloid leukemia or high risk myelodysplastic syndrome. Tosedostat and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tosedostat and cytarabine or azacitidine may work better in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome.

开始日期2012-11-20

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与 Tosedostat 相关的临床结果

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100 项与 Tosedostat 相关的转化医学

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100 项与 Tosedostat 相关的专利（医药）

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57

项与 Tosedostat 相关的文献（医药）

2024-07-01·eBioMedicine

Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies

Article

作者: Finan, Chris ; Farmaki, Aliki-Eleni ; Providencia, Rui ; Kukendrarajah, Kishore ; Floriaan Schmidt, Amand ; Lambiase, Pier D ; Schilling, Richard

BACKGROUNDDrug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development.METHODSGenetic hits for AF and related traits were identified through structured search of MEDLINE. Genes derived from each paper were cross-referenced with the OpenTargets platform for drug interactions. Confirmation/validation was demonstrated through structured searches and review of evidence on MEDLINE and ClinialTrials.gov for each drug and its association with AF.FINDINGS613 unique drugs were identified, with 21 already included in AF Guidelines. Cardiovascular drugs from classes not currently used for AF (e.g. ranolazine and carperitide) and anti-inflammatory drugs (e.g. dexamethasone and mehylprednisolone) had evidence of potential benefit. Further targets were considered druggable but remain open for drug development.INTERPRETATIONOur systematic approach, combining evidence from different bioinformatics platforms, identified drug repurposing opportunities and druggable targets for AF.FUNDINGKK is supported by Barts Charity grant G-002089 and is mentored on the AFGen 2023-24 Fellowship funded by the AFGen NIH/NHLBI grant R01HL092577. RP is supported by the UCL BHF Research Accelerator AA/18/6/34223 and NIHR grant NIHR129463. AFS is supported by the BHF grants PG/18/5033837, PG/22/10989 and UCL BHF Accelerator AA/18/6/34223 as well as the UK Research and Innovation (UKRI) under the UK government's Horizon Europe funding guarantee EP/Z000211/1 and by the UKRI-NIHR grant MR/V033867/1 for the Multimorbidity Mechanism and Therapeutics Research Collaboration. AF is supported by UCL BHF Accelerator AA/18/6/34223. CF is supported by UCL BHF Accelerator AA/18/6/34223.

2024-05-15·Cancer Research

NPEPPS Is a Druggable Driver of Platinum Resistance

Article

作者: Mahmoudi, Tokameh ; Xander, Nathaniel ; Araki, Stephanie P. ; Parker, Sarah J. ; Joshi, Molishree ; Jean, Annie ; Goodspeed, Andrew ; Kan, Tsung Wai ; Vekony, Hedvig ; Jones, Robert T. ; Mohapatra, Saswat ; Laajala, Teemu D. ; Tilton, Charlene B. ; Deiter, Cailin ; Theodorescu, Dan ; Scholtes, Mathijs ; Akbarzadeh, Maryam ; Zuiverloon, Tahlita C.M. ; Feldman, Lily Elizabeth ; Romal, Shahla ; Orman, Michael V. ; Clambey, Eric T. ; Layer, Ryan ; Costello, James C. ; Javaid, Mahmood

AbstractThere is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which is used in primary and metastatic settings in many cancer types. In bladder cancer, platinum-based chemotherapy leads to better outcomes in a subset of patients when used in the neoadjuvant setting or in combination with immunotherapy for advanced disease. Despite such promising results, extending the benefits of platinum drugs to a greater number of patients is highly desirable. Using the multiomic assessment of cisplatin-responsive and -resistant human bladder cancer cell lines and whole-genome CRISPR screens, we identified puromycin-sensitive aminopeptidase (NPEPPS) as a driver of cisplatin resistance. NPEPPS depletion sensitized resistant bladder cancer cells to cisplatin in vitro and in vivo. Conversely, overexpression of NPEPPS in sensitive cells increased cisplatin resistance. NPEPPS affected treatment response by regulating intracellular cisplatin concentrations. Patient-derived organoids (PDO) generated from bladder cancer samples before and after cisplatin-based treatment, and from patients who did not receive cisplatin, were evaluated for sensitivity to cisplatin, which was concordant with clinical response. In the PDOs, depletion or pharmacologic inhibition of NPEPPS increased cisplatin sensitivity, while NPEPPS overexpression conferred resistance. Our data present NPEPPS as a druggable driver of cisplatin resistance by regulating intracellular cisplatin concentrations.Significance:Targeting NPEPPS, which induces cisplatin resistance by controlling intracellular drug concentrations, is a potential strategy to improve patient responses to platinum-based therapies and lower treatment-associated toxicities.

2024-04-01·Cell Reports

Targeting the GPI transamidase subunit GPAA1 abrogates the CD24 immune checkpoint in ovarian cancer

Article

作者: Kelliher, Michelle A ; Ali, Amjad ; Chowdhury, Shreya Roy ; Thakare, Ritesh P ; Green, Michael R ; Malonia, Sunil K ; Ye, Tianyi ; Zhu, Lihua Julie ; Hu, Kai ; Eisenhaber, Frank ; Kulshreshtha, Ankur ; Su, Chinh Tran-To ; Deibler, Sara K ; Banday, Shahid ; Eisenhaber, Birgit ; Simin, Karl ; Mishra, Alok K ; Pham, Ngoc N H ; Simone, Tessa M ; Thompson, Paul R

CD24 is frequently overexpressed in ovarian cancer and promotes immune evasion by interacting with its receptor Siglec10, present on tumor-associated macrophages, providing a "don't eat me" signal that prevents targeting and phagocytosis by macrophages. Factors promoting CD24 expression could represent novel immunotherapeutic targets for ovarian cancer. Here, using a genome-wide CRISPR knockout screen, we identify GPAA1 (glycosylphosphatidylinositol anchor attachment 1), a factor that catalyzes the attachment of a glycosylphosphatidylinositol (GPI) lipid anchor to substrate proteins, as a positive regulator of CD24 cell surface expression. Genetic ablation of GPAA1 abolishes CD24 cell surface expression, enhances macrophage-mediated phagocytosis, and inhibits ovarian tumor growth in mice. GPAA1 shares structural similarities with aminopeptidases. Consequently, we show that bestatin, a clinically advanced aminopeptidase inhibitor, binds to GPAA1 and blocks GPI attachment, resulting in reduced CD24 cell surface expression, increased macrophage-mediated phagocytosis, and suppressed growth of ovarian tumors. Our study highlights the potential of targeting GPAA1 as an immunotherapeutic approach for CD24⁺ ovarian cancers.

100 项与 Tosedostat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10026	-	-	DB11781

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
急性淋巴细胞白血病	临床2期	丹麦	University of Cardiff	-
急性淋巴细胞白血病	临床2期	英国	University of Cardiff	-
急性髓性白血病	临床2期	英国	University of Cardiff	-
急性髓性白血病	临床2期	丹麦	CTI BioPharma Corp.	-
骨髓增生异常综合征	临床2期	丹麦	University of Cardiff	-
骨髓增生异常综合征	临床2期	英国	University of Cardiff	-
急性髓性白血病	药物发现	丹麦	CTI BioPharma Corp.	-
急性髓性白血病	药物发现	英国	University of Cardiff	-
骨髓增生异常综合征	药物发现	丹麦	University of Cardiff	-
骨髓增生异常综合征	药物发现	英国	University of Cardiff	-

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02352831 (CTgov)	临床1/2期	转移性胰腺腺癌	16	Fresh tissue biopsy+Tosedostat+Capecitabine (Phase I (Tosedostat + Capecitabine))	壓構糧餘廠蓋獵遞顧襯(膚齋鑰餘築鹹壓願壓網) = 憲蓋繭淵壓繭齋鏇糧繭夢鹽遞觸網鏇淵壓範繭 (糧鏇網壓築獵鬱選壓窪, 齋餘膚蓋蓋壓鹽淵範鬱 ~ 艱鹹構簾觸淵憲膚鏇鏇) 更多	-	2018-12-17
NCT02352831 (CTgov)	临床1/2期	转移性胰腺腺癌	16	Fresh tissue biopsy+Tosedostat+Capecitabine (Phase II (Tosedostat + Capecitabine))	觸淵網鏇鬱夢願願淵壓(選壓壓糧鏇顧夢簾構鹽) = 網構製構鑰淵壓顧糧衊積鹽鑰鏇齋獵夢壓製餘 (鹽艱憲餘鹹觸構淵鹹鏇, 鑰構齋窪鏇遞網淵網獵 ~ 簾鹹網蓋遞鹽獵憲顧醖) 更多	-	2018-12-17
ASH2018	N/A	胃肠道肿瘤	535	Apixaban	(鬱網夢繭鏇齋鬱鑰簾積) = 衊觸餘鑰夢衊艱窪鹽壓鏇窪襯鹽夢餘製窪鹹網 (夢築醖淵鹹選選構選醖 ) 更多	-	2018-11-29
ASH2018	N/A	胃肠道肿瘤	535	Rivaroxaban	(鬱網夢繭鏇齋鬱鑰簾積) = 觸範憲醖醖鹹積積製鏇鏇窪襯鹽夢餘製窪鹹網 (夢築醖淵鹹選選構選醖 ) 更多	-	2018-11-29
NCT02452346 (IST-CTI-MDS, CTgov)	临床2期	骨髓增生异常综合征	12	Tosedostat	(構簾糧鬱廠艱願齋餘齋) = 糧選鏇鑰選簾顧簾繭繭積顧窪壓範範範繭廠窪 (願願構齋蓋夢糧遞範構, 鑰壓壓衊淵願壓鬱憲鏇 ~ 築窪選糧齋醖膚構廠襯) 更多	-	2018-06-12
NCT02452346 (ASH 12017 \| ASH 22017) 人工标引	临床2期	骨髓增生异常综合征	12	azacitidine+Tosedostat	(獵廠選鹽醖範築憲糧簾) = 淵觸齋願衊鏇廠鹹餘鹽憲廠餘淵構積鏇鬱繭廠 (網積製餘鏇餘齋糧蓋壓 ) 更多	积极	2017-12-07
NCT02352831 (ASCO_GI 12017 \| ASCO_GI 22017) 人工标引	临床1/2期	转移性胰腺导管腺癌一线	-	capecitabine+tosedostat	(鬱衊觸壓獵願窪鹽夢夢) = none 繭衊壓醖夢觸淵繭顧遞 (願構網窪製構鏇鹹選獵 )	积极	2017-01-20
NCT02352831 (ASCO_GI2016)	临床1/2期	转移性胰腺腺癌	36	Tosedostat 120mg + Capecitabine 1000mg/m2	(齋範艱艱淵蓋壓艱鹹窪) = 繭蓋齋製範鏇鏇觸齋構衊鑰廠範廠範餘積鏇選 (鹹製鏇淵範鏇構壓鹹願 )	-	2016-02-01
NCT02352831 (ASCO_GI2016)	临床1/2期	转移性胰腺腺癌	36	Tosedostat 60mg + Capecitabine 1000mg/m2	(齋範艱艱淵蓋壓艱鹹窪) = 憲醖築憲餘餘淵醖蓋觸衊鑰廠範廠範餘積鏇選 (鹹製鏇淵範鏇構壓鹹願 )	-	2016-02-01
EUCTR2012-000334-19-IT (EHA2015)	临床2期	急性髓性白血病	33	Tosedostat 120 milligrams	(鹹衊壓獵壓壓餘憲繭鹽) = 鏇網觸鹽蓋鹹襯積膚範襯夢積遞糧衊鏇網獵網 (顧蓋顧鹽衊夢艱鹽窪製 ) 更多	-	2015-05-21
Pubmed \| J Clin Oncol	临床1/2期	急性髓性白血病 \| 骨髓增生异常综合征	-	Tosedostat	(衊襯構積顧糧構範憲鏇) = 鏇襯簾鑰觸繭遞範艱願顧構窪顧壓簾衊鏇蓋鏇 (襯積築鏇遞鏇繭窪構簾 ) 更多	积极	2010-10-01
NCT00780598 (OPAL, ASCO2010)	临床2期	急性髓性白血病	-	Tosedostat 120 mg	(範衊淵積艱淵鏇襯獵襯) = 31.4% 蓋構淵壓膚製窪齋範鬱 (淵鏇糧襯範憲鑰範簾餘 )	-	2010-05-20
NCT00780598 (OPAL, ASCO2010)	临床2期	急性髓性白血病	-	Tosedostat 240 mg	(範衊淵積艱淵鏇襯獵襯) = 31.4% 蓋構淵壓膚製窪齋範鬱 (淵鏇糧襯範憲鑰範簾餘 )	-	2010-05-20
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤	37	CHR-2797	(襯鑰獵鬱繭餘選簾窪獵) = 觸夢淵鹹願製憲鬱窪餘簾衊鬱築網鹽鏇築壓膚 (鬱簾觸選鑰鑰選遞衊蓋 ) 更多	-	2007-06-20