Delving into the Latest Updates on Zoptarelin Doxorubicin with Synapse

Overview

Basic Info

Drug Type

Peptide drug conjugates

Synonyms

Zoptarelin Doxorubicin Acetate, Zoptrex

+ [3]

Target

GnRHR x Top II

Mechanism

GnRHR agonists(Gonadotropin-releasing hormone receptor agonists), Top II inhibitors(Topoisomerase II inhibitors)

Therapeutic Areas

NeoplasmsUrogenital DiseasesEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Endometrial CarcinomaLocally Advanced Urothelial CarcinomaMetastatic castration-resistant prostate cancer+ [4]

Originator Organization

Tulane University Hospital & Clinic

Active Organization-

Inactive Organization

Æterna Zentaris, Inc.

Tulane University Hospital & Clinic

China National Pharmaceutical Group Co., Ltd.

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC91H117N19O26

InChIKeyOOUACICUAVTCEC-LZHWUUGESA-N

CAS Registry139570-93-7

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Gene Sequence

Sequence Code 14109089

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This is a therapeutic exploratory Phase 2 study evaluating AEZS-108 compared to standard single agent cytotoxic chemotherapy (SSCC) as measured by the median time of progression-free survival (PFS) in patients with chemotherapy refractory triple negative (ER/PR/HER2-negative) LHRH-R positive metastatic breast cancer.

Start Date01 Dec 2012

Sponsor / Collaborator

Æterna Zentaris, Inc.

EUCTR2012-000134-19-DE / Not yet recruitingNot Applicable

A randomised, phase 2 trial of AEZS-108 in chemotherapy refractory triple negative (ER/PR/HER2-negative) LHRH-R positive metastatic breast cancer - AEZS-108 in patients with LHRH receptor positive breast cancer

Start Date07 Sep 2012

Sponsor / Collaborator

AEterna Zentaris GmbH

100 Clinical Results associated with Zoptarelin Doxorubicin

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100 Translational Medicine associated with Zoptarelin Doxorubicin

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100 Patents (Medical) associated with Zoptarelin Doxorubicin

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58

Literatures (Medical) associated with Zoptarelin Doxorubicin

01 Apr 2024·Chemical Biology & Drug Design

Cytotoxic activity and cell specificity of a novel LHRH peptide drug conjugate, D‐Cys6‐LHRH vedotin, against ovarian cancer cell lines

Article

Author: Koh, Xiaoying ; Ke, Zhiyuan ; Lee, May Ann ; Wang, Sifang ; Vankadara, Subramanyam ; Chia, C S Brian ; Gunaratne, Jayantha ; Foo, Sin Yun

AbstractOvarian cancer is the most deadly female gynaecological malignancy in developed countries and new treatments are urgently needed. The luteinising hormone releasing hormone (LHRH) peptide drug conjugate Zoptarelin doxorubicin is one such potential new drug modality that entered clinical trials for treating LHRH receptor‐positive gynaecological cancers. However, development stopped after disappointing Phase 3 results in 2017. We believe the lack of efficacy was due to linker instability and payload potency. In this work, we replaced its linker‐toxin with vedotin (MC‐VC‐PABC‐MMAE), yielding the novel peptide drug conjugate D‐Cys6‐LHRH vedotin. A GI50 and cell specificity comparison against cancerous and non‐cancerous ovarian cell lines showed significantly superior bioactivity and selectivity over Zoptarelin doxorubicin (GI50 4 vs. 453 nM) and other chemotherapeutic drugs used for treating ovarian cancers. Our results suggest D‐Cys6‐LHRH vedotin can potentially be used as a treatment for ovarian cancer.

14 Jan 2020·Oncotarget

The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

Article

Author: Schally, Andrew ; Sipos, Eva ; Olah, Gabor ; Fodor, Klara ; Halmos, Gabor ; Dobos, Nikoletta ; Szekvolgyi, Lorant ; Steiber, Zita

Uveal melanoma (UM) is the most common malignant tumor of the eye. Recently, we have established that 46% of UM specimens express LHRH receptors. This finding supports the idea of a LHRH receptor-targeted therapy of UM patients. Cytotoxic analog of LHRH, AEZS-108 exhibits effective anti-cancer activity in LHRH-receptor positive cancers. AEZS-108 is a hybrid molecule, composed of a synthetic peptide carrier and the cytotoxic doxorubicin (DOX). In the present study, we investigated AEZS-108 induced cytotoxicity and the altered mRNA expression profile of regulatory factors related to angiogenesis and metastasis in LHRH receptor positive OCM3 cells. Our results show that AEZS-108 upregulates the expression of MASPIN/SERPINB5 tumor suppressor gene, which is downregulated in normal uvea and UM specimens independently from the LHRH receptor-ligand interaction. AEZS-108 also substantially downregulates hypoxia-inducible factor 1 alpha (HIF1A) expression. In order to investigate the mechanism of the induction of MASPIN by AEZS-108, OCM3 cells were treated with free DOX, D-Lys⁶ LHRH analog, or AEZS-108. qRT- PCR analysis revealed in OCM3 cells that AEZS-108 is a more potent inducer of MASPIN than free DOX. In conclusion, we show for the first time that AEZS-108 has a major impact in the regulation of angiogenesis thus plays a potential role in tumor suppression. Taken together, our results support the development of novel therapeutic strategies for UM focusing on LHRH receptors.

01 Jul 2019·Journal of Obstetrics and Gynaecology ResearchQ4 · MEDICINE

Inhibition of aerobic glycolysis enhances the anti‐tumor efficacy of Zoptarelin Doxorubicin in triple‐negative breast cancer cells

Q4 · MEDICINE

Article

Author: Wokoun, Ulrike ; Emons, Günter ; Hellriegel, Martin ; Gründker, Carsten

AbstractAimA characteristic of cancer cells including triple‐negative breast cancers (TNBC) is an increased aerobic glycolysis for ATP production representing a selective therapeutic target. More than 70% of TNBC express gonadotropin‐releasing hormone receptors (GnRH‐R). These receptors can be used for targeted chemotherapy with cytotoxic GnRH agonists such as Zoptarelin Doxorubicin, in which doxorubicin is covalently linked to [D‐Lys6]GnRH. In this study, we have analyzed whether inhibition of aerobic glycolysis can enhance the antitumor efficacy of GnRH‐R‐targeted chemotherapy using Zoptarelin Doxorubicin.MethodsTriple‐negative breast cancers cell lines MDA‐MB‐231 and HCC1806 were treated with Zoptarelin Doxorubicin, glycolysis inhibitor 2‐deoxy‐D‐glucose (2DG) or the combination of both agents. Cell viability was measured using Alamar blue. Induction of apoptosis was quantified by measurement of loss of mitochondrial membrane potential. In vivo experiments were performed using nude mice bearing xenografted MDA‐MB‐231 tumors.ResultsTreatment of TNBC cells with Zoptarelin Doxorubicin or with 2DG resulted in a significant decrease of cell viability and a significant increase of apoptosis. Treatment with Zoptarelin Doxorubicin in combination with 2DG resulted in significantly reduced viability and enhanced apoptosis compared with single‐agent treatments. Combinational index (CI) analysis revealed the co‐treatment effect as a synergistic. The antitumor effects of Zoptarelin Doxorubicin or 2DG were confirmed in nude mice. The tumor reducing effects of Zoptarelin Doxorubicin were enhanced by combination with 2DG.ConclusionThe glycolytic phenotype of TNBC can be used to improve antitumor therapies. Co‐treatment of Zoptarelin Doxorubicin with glycolysis inhibitor 2DG might be a suitable therapeutic option for GnRH receptor‐positive TNBC.

100 Deals associated with Zoptarelin Doxorubicin

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Zoptarelin Doxorubicin	-	DB12755

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic endometrial cancer	Phase 3	NL	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	ES	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	CA	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	RU	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	UA	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	GB	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	BG	Æterna Zentaris, Inc.	01 Apr 2013
Metastatic endometrial cancer	Phase 3	IE	Æterna Zentaris, Inc.	01 Apr 2013
Endometrial Carcinoma	Phase 3	-	Tulane University Hospital & Clinic	-
Endometrial Carcinoma	Phase 3	-	China National Pharmaceutical Group Co., Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01767155 (ZoptEC, CTgov)	Phase 3	Metastatic endometrial cancer	511	AEZS-108 / zoptarelin doxorubicin (AEZS-108 / Zoptarelin Doxorubicin)	naubwvhimn(ottbrhcpzo) = ufdzurleez nrsfcovhsg (xzioroabqo, aubrnofbhx - ubgpruvoxq) View more	-	31 Jul 2018
NCT01767155 (ZoptEC, CTgov)	Phase 3	Metastatic endometrial cancer	511	Doxorubicin (Doxorubicin/ Standard Chemotherapy)	naubwvhimn(ottbrhcpzo) = icxwdowbgq nrsfcovhsg (xzioroabqo, ghnixpcgay - asetcwvcik) View more	-	31 Jul 2018
NCT01767155 (ZoptEC, ASCO2018) Manual	Phase 3	Endometrial Carcinoma Second line	511	AEZS-108	(staovdijeo) = fqliisgobm cxjurhakof (cidkzemhof ) View more	Negative	05 Jun 2018
NCT01767155 (ZoptEC, ASCO2018) Manual	Phase 3	Endometrial Carcinoma Second line	511	doxorubicin	(staovdijeo) = zobsyaksni cxjurhakof (cidkzemhof ) View more	Negative	05 Jun 2018
NCT01240629 (ASCO_GU2017) Manual	Phase 2	Castration-Resistant Prostatic Cancer Second line \| Third line	25	Zoptarelin Doxorubicin	(sgobbsemej) = wfmxpnvabj axkfmchwmn (twtqhtiobq ) View more	Positive	16 Feb 2017
NCT01234519 (ASCO2014)	Phase 1	Metastatic urothelial carcinoma	13	Zoptarelin doxorubicin	(guvyzzlrtd) = wuthnwvlst npqpscjjtw (oycjjchgqc )	-	20 May 2014
NCT01240629 (ASCO2013)	Phase 1	Castration-Resistant Prostatic Cancer	18	AEZS-108	(osgupblgzc) = bfnezoqfoa peuogvwzrq (wejthsyaoz )	-	20 May 2013
ASCO2010	Phase 2	Platinum-Resistant Ovarian Carcinoma	43	AEZS-108	(cxfcalvgko) = ntxwfxzpub layzgdoswm (mgegimpsnx ) View more	-	20 May 2010
ASCO2007	Phase 1	Neoplasms	-	ZEN-008	xijdavnwyh(nuvrmpiegu) = One pt at this dose level had an allergic skin reaction during infusion, subsequent cycles with anti-allergic pre-medication were tolerated ljphlwghhu (aymtaiiwnf ) View more	-	20 Jun 2007