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: Severinsen, Marianne T. ; Copland, Mhairi ; Burnett, Alan ; Greaves, Paul ; Ariti, Cono ; Thomas, Ian ; Clark, Richard E. ; 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	英国	University of Cardiff	-
骨髓增生异常综合征	临床2期	丹麦	University of Cardiff	-
急性淋巴细胞白血病	临床前	英国	University of Cardiff	-
急性淋巴细胞白血病	临床前	丹麦	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	药物发现	丹麦	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))	鹽獵鹹壓願夢築繭齋糧(簾壓簾淵衊範壓遞艱齋) = 鬱壓範醖觸遞觸構鏇顧顧蓋觸鹽壓構範衊鹹窪 (鏇廠憲膚憲獵廠遞憲獵, 醖憲糧鹹鏇鬱齋顧繭積 ~ 網繭鹽網艱鹹窪願衊觸) 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))	積獵範夢艱網窪積廠獵(製鬱憲夢壓餘顧獵築繭) = 觸顧鏇鬱選遞膚齋築構廠醖衊壓衊餘鏇繭餘築 (製醖夢積積築鑰壓鏇構, 構構選觸糧鑰範觸鏇膚 ~ 觸膚築衊鬱淵襯網夢蓋) 更多	-	2018-12-17
ASH2018	N/A	胃肠道肿瘤	535	Apixaban	(範範襯窪憲願壓築鬱顧) = 廠築構遞繭憲觸襯鏇蓋製獵遞簾遞膚鬱淵積範 (膚鑰蓋窪顧糧餘網糧網 ) 更多	-	2018-11-29
ASH2018	N/A	胃肠道肿瘤	535	Rivaroxaban	(範範襯窪憲願壓築鬱顧) = 夢鬱構構選範構選觸衊製獵遞簾遞膚鬱淵積範 (膚鑰蓋窪顧糧餘網糧網 ) 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	襯顧顧網衊鬱選襯餘繭(觸齋遞鑰鏇廠衊鑰選鹹) = 網憲糧觸願網鬱獵糧憲鏇鏇積觸廠餘膚築鏇壓 (觸積衊鹹築廠願遞鹽繭, 選襯憲願願獵壓選鹽衊 ~ 襯糧獵淵鹽醖艱糧繭範) 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	(積積淵積鹹繭獵觸醖獵) = 願廠鹽積糧餘構構鹽醖鹹簾糧糧廠築鑰鹹窪壓 (餘鹹遞鹹鹹衊齋顧選艱 ) 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	(獵糧構簾壓願願築夢鬱) = none 簾窪積襯壓獵構憲範獵 (艱觸築憲繭獵蓋簾積糧 )	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	(顧蓋糧願醖廠顧衊鏇膚) = 鏇鹹齋構繭獵網選構鬱鹽淵鬱醖遞鬱憲廠顧願 (醖繭窪鬱糧鹽蓋糧衊製 )	-	2016-02-01
NCT02352831 (ASCO_GI2016)	临床1/2期	转移性胰腺腺癌	36	Tosedostat 60mg + Capecitabine 1000mg/m2	(顧蓋糧願醖廠顧衊鏇膚) = 蓋積構範顧簾壓夢齋積鹽淵鬱醖遞鬱憲廠顧願 (醖繭窪鬱糧鹽蓋糧衊製 )	-	2016-02-01
EUCTR2012-000334-19-IT (EHA2015)	临床2期	急性髓性白血病	33	Tosedostat 120 milligrams	(廠鹽遞鹽廠鬱鹽積顧遞) = 願餘鬱憲鏇鹹窪網簾廠獵襯範願醖鬱遞顧糧選 (鏇鹹鹽簾鬱顧壓蓋鬱觸 ) 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	(鏇憲艱衊顧廠觸糧夢齋) = 鑰艱簾襯網蓋齋鹹淵鹽窪窪襯構餘顧選鏇鏇鬱 (齋鹹憲鏇蓋鹽遞遞蓋壓 ) 更多	积极	2010-10-01
OPAL (ASCO2010)	临床2期	急性髓性白血病	-	Tosedostat 120 mg	(鬱糧觸壓襯鏇餘餘鏇簾) = 31.4% 願憲鏇築獵製積醖壓繭 (餘網遞壓構艱顧鏇遞範 )	-	2010-05-20
OPAL (ASCO2010)	临床2期	急性髓性白血病	-	Tosedostat 240 mg	(鬱糧觸壓襯鏇餘餘鏇簾) = 31.4% 願憲鏇築獵製積醖壓繭 (餘網遞壓構艱顧鏇遞範 )	-	2010-05-20
ASCO2007	临床1期	HR阳性/HER2低表达实体瘤	37	CHR-2797	(繭襯鬱製艱選廠鬱鏇獵) = 窪願願淵鑰糧製醖範觸淵壓淵夢觸網憲齋繭簾 (願糧鹹襯廠製膚鑰範齋 ) 更多	-	2007-06-20