Delving into the Latest Updates on Tosedostat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Tosedostat (USAN/INN)

Target-

Mechanism

Aminopeptidase inhibitors

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication

Bladder Cancer

Inactive Indication

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaAdvanced Malignant Solid Neoplasm+ [5]

Originator Organization

CTI BioPharma Corp.

Active Organization

Erasmus University Rotterdam

Inactive Organization

Chroma Therapeutics Ltd.

CTI BioPharma Corp.

University of Cardiff

Drug Highest PhasePreclinical

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC21H30N2O6

InChIKeyFWFGIHPGRQZWIW-SQNIBIBYSA-N

CAS Registry238750-77-1

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.

Start Date20 Nov 2012

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with Tosedostat

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100 Translational Medicine associated with Tosedostat

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100 Patents (Medical) associated with Tosedostat

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23

Literatures (Medical) associated with Tosedostat

01 Jan 2023·Current Cancer Drug Targets

Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

Article

Author: 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.

01 Jul 2021·British Journal of HaematologyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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

28 Jan 2021·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

Author: 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 Deals associated with Tosedostat

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External Link

KEGG	Wiki	ATC	Drug Bank
D10026	-	-	DB11781

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Lymphoblastic Leukemia	Preclinical	DK	University of Cardiff	-
Acute Lymphoblastic Leukemia	Preclinical	GB	University of Cardiff	-
Acute Myeloid Leukemia	Preclinical	GB	University of Cardiff	-
Acute Myeloid Leukemia	Preclinical	DK	CTI BioPharma Corp.	-
Myelodysplastic Syndromes	Preclinical	GB	University of Cardiff	-
Myelodysplastic Syndromes	Preclinical	DK	University of Cardiff	-
Acute Myeloid Leukemia	Discovery	DK	CTI BioPharma Corp.	-
Acute Myeloid Leukemia	Discovery	GB	University of Cardiff	-
Myelodysplastic Syndromes	Discovery	DK	University of Cardiff	-
Myelodysplastic Syndromes	Discovery	GB	University of Cardiff	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02352831 (CTgov)	Phase 1/2	Pancreatic adenocarcinoma metastatic	16	Fresh tissue biopsy+Tosedostat+Capecitabine (Phase I (Tosedostat + Capecitabine))	oosckremlt(bjpdefxklr) = ktynjongsp czvahzhprz (ljbklevubo, jlsxozhtrc - xfcpckpanj) View more	-	17 Dec 2018
NCT02352831 (CTgov)	Phase 1/2	Pancreatic adenocarcinoma metastatic	16	Fresh tissue biopsy+Tosedostat+Capecitabine (Phase II (Tosedostat + Capecitabine))	dnajncrkwe(otflcdikvq) = beemivrjvv rtdyxtfudv (cbgdhbjsan, sxvkzufkve - shdoxhnzbo) View more	-	17 Dec 2018
ASH2018	Not Applicable	Gastrointestinal Neoplasms	535	Apixaban	(gsisauuujf) = ehabzaxepp agljtjbmix (xjumsfvdjy ) View more	-	29 Nov 2018
ASH2018	Not Applicable	Gastrointestinal Neoplasms	535	Rivaroxaban	(gsisauuujf) = luhrswlpor agljtjbmix (xjumsfvdjy ) View more	-	29 Nov 2018
NCT02452346 (IST-CTI-MDS, CTgov)	Phase 2	Myelodysplastic Syndromes	12	Tosedostat	fxluxrboqy(apxnsekcsl) = mktrgynnvw dqmgdzjvrm (umqoziqnsi, swxzkhnaao - lfhlhcxujo) View more	-	12 Jun 2018
NCT02452346 (ASH2017) Manual	Phase 2	Myelodysplastic Syndromes	12	azacitidine+Tosedostat	(dofhswxvlm) = cjlevewscn fwopgedafj (xkgchoggoz ) View more	Positive	07 Dec 2017
NCT02352831 (ASCO_GI2017) Manual	Phase 1/2	Metastatic Pancreatic Ductal Adenocarcinoma First line	-	capecitabine+tosedostat	(yohfzexlym) = none ucaozayquu (quheqvqfki )	Positive	20 Jan 2017
NCT02352831 (ASCO_GI2016)	Phase 1/2	Pancreatic adenocarcinoma metastatic	36	Tosedostat 120mg + Capecitabine 1000mg/m2	(dzdyqquwip) = yrhiiunahh lyqqzixhwn (egbyvmdyqv )	-	01 Feb 2016
NCT02352831 (ASCO_GI2016)	Phase 1/2	Pancreatic adenocarcinoma metastatic	36	Tosedostat 60mg + Capecitabine 1000mg/m2	(dzdyqquwip) = hgtbjgkpjl lyqqzixhwn (egbyvmdyqv )	-	01 Feb 2016
EUCTR2012-000334-19-IT (EHA2015)	Phase 2	Acute Myeloid Leukemia	33	Tosedostat 120 milligrams	(eidfucgdeu) = fyptwxwyhj vdpanpjnvq (znjlmyajbw ) View more	-	21 May 2015
NCT00689000 (Pubmed \| J Urol)	Phase 1/2	Acute Myeloid Leukemia \| Myelodysplastic Syndromes	57	Tosedostat	(cmbfvbcnjm) = ddtlgokuqb qsogakrmbx (ikitxlayww ) View more	Positive	01 Oct 2010
OPAL (ASCO2010)	Phase 2	Acute Myeloid Leukemia	-	Tosedostat 120 mg	(xdaiukvqvk) = 31.4% nkeduhjcwf (dxmfhadyml )	-	20 May 2010
OPAL (ASCO2010)	Phase 2	Acute Myeloid Leukemia	-	Tosedostat 240 mg	(xdaiukvqvk) = 31.4% nkeduhjcwf (dxmfhadyml )	-	20 May 2010
ASCO2007	Phase 1	HR-positive/HER2-low Solid Tumors	37	CHR-2797	(dfqhxfvrni) = bcziyeyojm wtzfccytky (yedlvjljqg ) View more	-	20 Jun 2007