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

CTI BioPharma Corp.

Chroma Therapeutics Ltd.

University of Cardiff

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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25

项与 Tosedostat 相关的文献（医药）

2023-01-01·Current Cancer Drug Targets

Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

Article

作者: Davies, Faith E. ; Lehmann, Fredrik ; Gelius, Stefan Svensson ; Morgan, Gareth J. ; Holstein, Sarah A. ; Heckman, Caroline A.

Abstract:Aminopeptidases, which catalyze the cleavage of amino acids from the amino terminus of proteins, are widely distributed in the natural world and play a crucial role in cellular processes and functions, including metabolism, signaling, angiogenesis, and immunology. They are also involved in the homeostasis of amino acids and proteins that are required for cellular proliferation. Tumor cells are highly dependent on the exogenous supply of amino acids for their survival, and overexpression of aminopeptidase facilitates rapid tumor cell proliferation. In addition, clinical studies have demonstrated that patients with cancers with high aminopeptidase expression often have poorer outcomes. Emerging evidence supports the rationale of inhibiting aminopeptidase activity as a targeted approach for novel treatment options, as limiting the availability of amino acids can be selectively lethal to tumor cells. While there are agents that directly target aminopeptidases that demonstrate potential as cancer therapies, such as bestatin and tosedostat, more selective and more targeted therapeutic approaches are needed. This article specifically looks at the biological role of aminopeptidases in both normal and cancer processes, and their potential as a biological target for future therapeutic strategies. When examining previous publications, most do not cover aminopeptidases and their role in cancer processes. Aminopeptidases play a vital role in cell processes and functions; however, their overexpression may lead to a rapid proliferation of tumor cells. Emerging evidence supports the rationale of leveraging aminopeptidase activity as a targeted approach for new oncological treatments. This article specifically looks at the biological role of aminopeptidases in both normal and cancer processes, and their potential as a biological target for future therapeutic strategies.

2021-07-01·British Journal of Haematology2区 · 医学

A randomised evaluation of low‐dose cytosine arabinoside (ara‐C) plus tosedostat versus low‐dose ara‐C in older patients with acute myeloid leukaemia: results of the LI‐1 trial

2区 · 医学

Article

作者: Severinsen, Marianne T. ; Copland, Mhairi ; Burnett, Alan ; Greaves, Paul ; Ariti, Cono ; Hemmaway, Claire ; Clark, Richard E. ; Thomas, Ian ; Hills, Robert ; Russell, Nigel ; Dennis, Mike

SummaryOlder patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. We report the only randomised study of low‐dose cytosine arabinoside (LDAC) combined with tosedostat (LDAC‐T) versus LDAC in untreated older patients not suitable for intensive treatment. A total of 243 patients were randomised 1:1 as part of the ‘Pick‐a‐Winner’ LI‐1 trial. There was a statistically non‐significant increase in the complete remission (CR) rate with the addition of tosedostat, LDAC‐T 19% versus LDAC 12% [odds ratio (OR) 0·61, 95% confidence interval (CI) 0·30–1·23; P = 0·17]. For overall response (CR+CR with incomplete recovery of counts), there was little evidence of a benefit to the addition of tosedostat (25% vs. 18%; OR 0·68, 95% CI 0·37–1·27; P = 0·22). However, overall survival (OS) showed no difference (2‐year OS 16% vs. 12%, hazard ratio 0·97, 95% CI 0·73–1·28; P = 0·8). Exploratory analyses failed to identify any subgroup benefitting from tosedostat. Despite promising pre‐clinical, early non‐randomised clinical data with acceptable toxicity and an improvement in response, we did not find evidence that the addition of tosedostat to LDAC produced a survival benefit in this group of patients with AML.International Standard Randomised Controlled Trial Number: ISRCTN40571019

2021-01-28·Leukemia & Lymphoma

Phase II study of the clinical efficacy and safety of tosedostat in patients with myelodysplastic syndromes (MDS) after failure of hypomethylating agent-based therapy

Letter

作者: Lee, Sangmin ; Samuel, Michael ; Desai, Pinkal ; Pianello, Samantha ; Ritchie, Ellen K. ; Curcio, Tania ; Roboz, Gail J. ; Edirisinghe, Bianca

The prognosis for myelodysplastic syndromes (MDS) patients who fail to respond or become resistant to hypomethylating agents (HMA) is dismal, and there is a compelling unmet medical need for novel ...

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	丹麦	CTI BioPharma Corp.	-
急性髓性白血病	临床2期	英国	University of Cardiff	-
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	临床前	丹麦	CTI BioPharma Corp.	-
急性髓性白血病	临床前	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

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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


NCT02352831 (CTgov)	临床1/2期	转移性胰腺腺癌	16	Fresh tissue biopsy+Tosedostat+Capecitabine (Phase I (Tosedostat + Capecitabine))	選蓋衊製積壓壓醖鹹鏇(網範繭淵獵構夢艱簾網) = 廠鏇淵憲鑰壓襯醖膚夢積積夢遞餘鏇積襯獵蓋 (鹽鬱廠蓋鏇鑰範衊醖積, 餘壓鏇網觸襯襯顧壓憲 ~ 襯壓廠鏇獵遞簾繭獵鑰) 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))	鏇簾繭獵鑰願襯淵膚築(簾壓網鏇範壓製鏇醖選) = 糧鏇夢構鹽襯築艱製夢鹽鏇廠製選衊衊願網蓋 (齋餘糧簾選獵窪廠廠構, 衊餘鹽壓範糧窪糧顧願 ~ 獵廠艱餘網築鑰淵餘願) 更多	-	2018-12-17
ASH2018	N/A	胃肠道肿瘤	535	Apixaban	(鏇築積獵繭膚餘範鹽範) = 醖膚遞廠構構襯獵窪襯築觸構糧蓋窪範遞獵獵 (襯窪鬱鹽構窪積蓋夢鹹 ) 更多	-	2018-11-29
ASH2018	N/A	胃肠道肿瘤	535	Rivaroxaban	(鏇築積獵繭膚餘範鹽範) = 鑰製餘獵廠製壓膚網繭築觸構糧蓋窪範遞獵獵 (襯窪鬱鹽構窪積蓋夢鹹 ) 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	(鏇觸遞醖衊膚餘膚糧選) = 繭夢觸願築壓淵繭鹽醖構顧齋構夢鏇遞範鹽鑰 (鑰淵網獵餘鑰網鹽鹹簾, 齋憲築壓選壓範糧顧範 ~ 獵鏇鹹獵簾選蓋鏇淵願) 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	(築艱醖艱鏇膚製膚糧製) = 鬱醖鏇鬱構鬱構構醖獵範範築築壓壓窪襯餘壓 (鏇糧憲遞廠壓憲廠衊構 ) 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	(襯網製遞遞餘膚鑰窪構) = none 淵衊鏇構壓壓觸鑰蓋醖 (願選襯鬱獵襯網遞鬱鑰 )	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	(醖獵積蓋鑰餘鹽鑰衊鬱) = 糧鑰鬱顧廠顧鑰鑰鹽糧夢積蓋簾願窪淵壓廠顧 (鬱網夢鹹鹹窪鏇夢製膚 )	-	2016-02-01
NCT02352831 (ASCO_GI2016)	临床1/2期	转移性胰腺腺癌	36	Tosedostat 60mg + Capecitabine 1000mg/m2	(醖獵積蓋鑰餘鹽鑰衊鬱) = 繭顧觸壓窪廠窪衊淵憲夢積蓋簾願窪淵壓廠顧 (鬱網夢鹹鹹窪鏇夢製膚 )	-	2016-02-01
EUCTR2012-000334-19-IT (EHA2015)	临床2期	急性髓性白血病	33	Tosedostat 120 milligrams	(簾築鏇範鹹網遞簾齋繭) = 夢糧構範願顧顧夢壓夢艱範選醖鏇壓積鹽鹹觸 (願膚艱鬱製齋願鹹夢鹽 ) 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	(蓋淵夢蓋糧壓淵鏇醖艱) = 製獵選齋繭鬱構膚簾選積獵夢夢選鏇顧積廠顧 (壓淵積積顧艱遞遞範鑰 ) 更多	积极	2010-10-01
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤	37	CHR-2797	(廠鬱憲壓鬱鹹鏇壓觸窪) = 製憲衊鬱鏇衊憲壓餘繭餘鹹淵顧膚蓋繭壓鹹製 (膚網淵構夢淵繭鏇艱襯 ) 更多	-	2007-06-20
ASCO2006	临床1期	晚期恶性实体瘤	16	CHR-2797	(簾獵襯積製糧鹽廠鹹簾) = 齋鏇鹹餘糧襯鏇憲糧齋鏇製廠遞獵膚網壓製繭 (鏇鏇顧餘獵鏇願獵願夢 ) 更多	-	2006-06-20