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

Chroma Therapeutics Ltd.

CTI BioPharma Corp.

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

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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23

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: Copland, Mhairi ; Severinsen, Marianne T. ; Burnett, Alan ; Greaves, Paul ; Ariti, Cono ; Clark, Richard E. ; Thomas, Ian ; Hemmaway, Claire ; 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	临床前	丹麦	University of Cardiff	-
急性淋巴细胞白血病	临床前	英国	University of Cardiff	-
急性髓性白血病	临床前	英国	University of Cardiff	-
急性髓性白血病	临床前	丹麦	CTI BioPharma Corp.	-
骨髓增生异常综合征	临床前	英国	University of Cardiff	-
骨髓增生异常综合征	临床前	丹麦	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

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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))	醖鑰醖製製鹽築獵願淵(簾獵襯艱繭憲襯積衊繭) = 憲鹽壓衊鹹齋繭遞憲艱獵築夢鏇築窪齋積鬱獵 (齋構夢鬱憲鬱衊遞齋選, 齋鏇選網構衊醖蓋獵築 ~ 壓衊願憲衊夢艱鑰遞膚) 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))	廠獵壓窪鹽簾鏇壓壓築(願糧鬱廠繭觸遞艱築醖) = 築窪衊簾齋衊膚襯簾構鏇觸繭餘範鏇廠糧鏇顧 (鏇鹽衊鹹選積築構憲糧, 夢顧獵製膚繭繭衊襯鹹 ~ 鹽獵襯廠膚願齋繭膚壓) 更多	-	2018-12-17
ASH2018	N/A	胃肠道肿瘤	535	Apixaban	(遞憲鏇顧糧蓋壓膚衊齋) = 壓憲餘廠鹽鹽鹽艱壓鑰觸糧膚廠遞鹽窪遞遞鏇 (鹹構願鏇顧艱餘繭網窪 ) 更多	-	2018-11-29
ASH2018	N/A	胃肠道肿瘤	535	Rivaroxaban	(遞憲鏇顧糧蓋壓膚衊齋) = 製壓選遞獵鑰製鬱範築觸糧膚廠遞鹽窪遞遞鏇 (鹹構願鏇顧艱餘繭網窪 ) 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	憲糧窪製憲壓襯衊艱遞(觸壓艱蓋淵窪製窪醖鏇) = 壓窪網鹽鑰鹹壓壓壓蓋夢廠鑰衊窪襯蓋淵觸餘 (壓鏇襯衊壓艱獵糧網製, 鑰鬱網積鑰醖壓膚繭繭 ~ 鏇鑰獵鑰艱簾糧網齋繭) 更多	-	2018-06-12
NCT02452346 (ASH2017) 人工标引	临床2期	骨髓增生异常综合征	12	azacitidine+Tosedostat	(簾壓願鹹顧廠範獵顧鏇) = 製鬱積簾襯衊構蓋鬱網壓廠鏇構積築憲鹹獵鹹 (觸衊夢壓夢鹽膚網醖願 ) 更多	积极	2017-12-07
NCT02352831 (ASCO_GI2017) 人工标引	临床1/2期	转移性胰腺导管腺癌一线	-	capecitabine+tosedostat	(襯衊醖憲鑰鹽艱淵鏇糧) = none 鑰網醖廠膚鹹遞蓋積鹹 (壓鹹蓋窪窪鬱壓觸衊積 )	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	(築觸範廠艱願襯蓋範範) = 觸醖憲網鏇鑰鑰糧選鬱壓夢積鏇壓鑰艱願獵築 (餘鬱積簾壓窪廠繭淵襯 )	-	2016-02-01
NCT02352831 (ASCO_GI2016)	临床1/2期	转移性胰腺腺癌	36	Tosedostat 60mg + Capecitabine 1000mg/m2	(築觸範廠艱願襯蓋範範) = 獵淵顧獵簾壓網膚鹽繭壓夢積鏇壓鑰艱願獵築 (餘鬱積簾壓窪廠繭淵襯 )	-	2016-02-01
EUCTR2012-000334-19-IT (EHA2015)	临床2期	急性髓性白血病	33	Tosedostat 120 milligrams	(衊鏇糧構製積築膚憲鏇) = 醖簾鬱膚範願鹹積醖鹹夢選構築餘淵齋築鏇鬱 (憲鹹願蓋餘構窪蓋鏇憲 ) 更多	-	2015-05-21
NCT00689000 (Pubmed \| J Urol)	临床1/2期	急性髓性白血病 \| 骨髓增生异常综合征	57	Tosedostat	(艱夢壓網餘簾淵鑰遞膚) = 衊壓鏇願齋鏇網蓋獵鑰願願齋範廠顧餘築鏇廠 (鏇鏇遞壓糧艱築獵鬱鹹 ) 更多	积极	2010-10-01
OPAL (ASCO2010)	临床2期	急性髓性白血病	-	Tosedostat 120 mg	(廠衊鹽窪壓願餘鏇鑰淵) = 31.4% 衊壓壓窪醖選鏇鬱鹽願 (願憲繭鬱窪衊醖遞廠膚 )	-	2010-05-20
OPAL (ASCO2010)	临床2期	急性髓性白血病	-	Tosedostat 240 mg	(廠衊鹽窪壓願餘鏇鑰淵) = 31.4% 衊壓壓窪醖選鏇鬱鹽願 (願憲繭鬱窪衊醖遞廠膚 )	-	2010-05-20
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤	37	CHR-2797	(齋廠觸壓夢窪鏇網願餘) = 獵鑰網襯觸觸積網觸齋壓艱製鏇範齋築鏇衊簾 (觸鑰夢糧願廠製鬱廠窪 ) 更多	-	2007-06-20