Delving into the Latest Updates on Irosustat with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

6-Oxo-8,9,10,11-Tetrahydro-7h-Cyclohepta[C][1]Benzopyran-3-O-Sulfamate, Irostustat, Irosustat (USAN/INN)

+ [8]

Target

STS

Action

inhibitors

Mechanism

STS inhibitors(Steryl-sulfatase inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesUrogenital Diseases+ [1]

Active Indication-

Inactive Indication

ER Positive Endometrial CarcinomaEstrogen receptor positive breast cancerHER2 Positive Breast Cancer+ [4]

Originator Organization

Ipsen SA

Active Organization-

Inactive Organization

Ipsen SA

Peter MacCallum Cancer Institute

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC14H15NO5S

InChIKeyDSLPMJSGSBLWRE-UHFFFAOYSA-N

CAS Registry288628-05-7

70% of breast cancers that occur in postmenopausal women rely on the hormone oestrogen to grow and are likely to respond to hormone treatment. This type of treatment reduces the amount of oestrogen in the body, slowing the growth of cancer or stopping it altogether. One type of hormone treatment, aromatase inhibitors (AIs), works by stopping the body from making oestrogen. Currently, women with locally advanced or metastatic breast cancer that is not being controlled by one class of AI are switched to the other class of AI. The reason for this is that some cancer cells can become resistant to one class but are still sensitive to the other class. However, oestrogen can be made in the body by two pathways and AIs block only one of these pathways. A new drug called Irosustat can reduce the production of oestrogen in the body by blocking the second pathway. This study is investigating whether adding Irosustat to AI treatment i.e. blocking both pathways at the same time, can further reduce the amount of oestrogen in the body and therefore control the breast cancer better.
27 postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer that is not being controlled by their current AI treatment will be recruited in this study from 9 United Kingdom (UK) hospitals. Eligible patients will receive 40mg of Irosustat once daily in addition to the AI on which they progressed. Patients will receive Irosustat for as long as it controls their cancer or until they have side effects that stop them from taking treatment. Patients will be seen monthly for the first 6 months and every 3 months thereafter. Participating patients will also be given the option to take part in the exploratory part of this study by donating tissue and blood samples.

Start Date01 Oct 2012

Sponsor / Collaborator

Imperial College London

[+1]

NCT01662726

/ TerminatedPhase 2IIT

A Phase II, Open Label, Preoperative Study to Assess the Efficacy of the Novel Steroid Sulfatase Inhibitor Irosustat in Postmenopausal Women With Early Oestrogen Receptor Positive Breast Cancer

This study is investigating the effects of a new hormone treatment for breast cancer called Irosustat. Seventy percent of breast cancers in post-menopausal wome rely on oestrogen to grow therefore are likely to respond to hormone therapy. Irosustat blocks a different pathway of steroid synthesis to Aromatase, reducing in this way oestrogen levels in the body. As less oestrogen reaches the breast cancer, it grows more slowly or stops growing altogether.
IPET will recruit postmenopausal women with early, hormone sensitive, treatment naive breast cancer will receive 40mg of Irosustat once daily for 2 weeks. The effects of Irosustat on breast cancer will be evaluated by PET scans (Positron Emission Tomography) using a radioactive substance called FLT as a tracer. The scans will be performed in a PET-CT scanner which combines a PET scan and a CT scan (Computer Tomography) into one scan. This type of scan can show how body tissues are working, as well as what they look like. FLT-PET scans will be performed before and following treatment with Irosustat. As cancer cells grow faster than the normal cells around them, they will take up more of the radioactive substance, and so stand out clearly on the scan. If Irosustat is slowing down the cancer growth, the cancer will take up less of the tracer.
Blood samples will be taken at regular intervals to assess what the new drug does to the body and the safety and tolerability of Irosustat will be assessed. The study incorporates translation aspects/endpoints which are based on the collection of tumour biopsies before and after treatment with Irosustat although the later biopsy is not mandatory.

Start Date01 Aug 2012

Sponsor / Collaborator

Imperial College London

[+5]

NCT01230970

/ TerminatedPhase 2

A Phase II, Open-label, Exploratory Study to Assess the Short Term Intratumoural and Peripheral Effects of BN83495 Administered for 14 Days Prior to Surgery to Postmenopausal Women With Newly Diagnosed Primary Invasive Oestrogen Receptor Positive Breast Cancer

This trial will assess the intratumoural pharmacological activity of BN83495 by changes in intratumoural levels of sex hormones and associated inhibition of steroid sulphatase (STS) activity.

Start Date01 May 2011

Sponsor / Collaborator

Ipsen SA

100 Clinical Results associated with Irosustat

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100 Translational Medicine associated with Irosustat

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100 Patents (Medical) associated with Irosustat

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89

Literatures (Medical) associated with Irosustat

12 Feb 2026·ACS Medicinal Chemistry Letters

Synthesis and Biological Evaluation of 3,5-Diaryl-Substituted 1,2,4-Oxadiazole Sulfamates as Potent Steroid Sulfatase Inhibitors

Article

Author: Szwarc-Karabyka, Katarzyna ; Rak, Janusz ; Daśko, Mateusz ; Czubak, Paweł ; Martyna, Aleksandra ; Masłyk, Maciej ; Biernacki, Karol ; Ciupak, Olga ; Grobelna, Agata ; Rachoń, Janusz ; Kubiński, Konrad ; Kwaśnik, Mateusz ; Demkowicz, Sebastian ; Mirocki, Artur

A novel series of 3,5-disubstituted 1,2,4-oxadiazole sulfamates was synthesized and evaluated as steroid sulfatase (STS) inhibitors. Molecular docking predicted high affinity (binding energies of up to -8.9 kcal·mol^-1), often surpassing the reference Irosustat. Biological evaluation confirmed potent inhibition; compound 9n reduced enzymatic STS activity to 3.5% at 10 μM. In JEG-3 cells, the most potent derivative, 9j, exhibited an IC₅₀ of 6.64 nM, comparable to that of Irosustat (4.19 nM). Structure-activity relationship analysis revealed that the substitution pattern of the oxadiazole heterocycle plays a decisive role in determining biological activity. Shifting the aryl-sulphamate pharmacophore between positions 3- and 5- of the 1,2,4-oxadiazole heterocycle is crucial for maintaining high biological activity. These findings establish 3,5-disubstituted 1,2,4-oxadiazole sulfamates as promising leads for treating hormone-dependent cancers.

01 Jan 2026·BREAST CANCER RESEARCH AND TREATMENT

Assessing endocrine resistance: monitoring circulating ESR1 mutations in Irosustat-treated ER positive breast cancer

Article

Author: Allsopp, Rebecca C ; Coombes, R Charles ; Palmieri, Carlo ; Luo, Jin-Li ; Wadsley, Marc K ; Page, Karen ; Acheampong, Emmanuel ; Hastings, Robert K ; Martinson, Luke J ; Shaw, Jacqueline A

Abstract:

Purpose:

We aimed to investigate the prevalence and spectrum of ESR1 mutations alongside cell-free DNA (cfDNA) dynamics in patients with estrogen receptor-positive metastatic breast cancer recruited to the phase II IRIS study who had progressed on first-line aromatase inhibitor (AI) therapy and then continued their AI in combination with Irusostat (40 mg), an irreversible steroid sulfatase inhibitor.

Methods:

cfDNA was isolated from 96 serial plasma samples from 24 patients, alongside primary tumour DNA ( n = 16), and analysed by next-generation sequencing using a custom-designed mutation panel on the Illumina NovaSeq platform.

Results:

Thirteen of 16 tumour DNA samples harboured at least one somatic mutation across nine genes. Twenty one of the 24 patients (88%) had at least one somatic mutation in cfDNA (248 total mutations across 10 genes). Circulating tumour DNA ESR1 mutations (ct ESR1 m) were the most prevalent, present in 16 patients (76%) with both stable (SD) and progressive disease (PD), showing no clear association with disease progression. Eleven patients had polyclonal ct ESR1 m within the ligand-binding domain, six at baseline, while five harboured a single ct ESR1 m variant. Five other patients acquired polyclonal mutations over treatment.

Conclusions:

Analysis of serial plasma samples revealed highly dynamic ct ESR1 m during AI treatment and frequent detection of polyclonal ct ESR1 m in patients (both with SD and PD) recruited to the IRIS study. These findings, albeit in a limited sample size, underscore the challenge of targeting a single ESR1 mutation and emphasise the need for careful patient selection, specifically those with wild-type ESR1 , in trials investigating sequential estrogen-lowering therapies.

01 Oct 2025·LIFE SCIENCES

Protective potential of Irosustat, STX140 and the sulfonate derivative 1G in counteracting cisplatin-induced renal and hepatic toxicities: An in vivo comparative study

Article

Author: Alsheikh Zain, Haya N ; Hassan, Hend M ; Hersi, Fatima ; Omar, Hany A ; Dohle, Wolfgang ; Shaker, Haidi A ; Anbar, Hanan S ; Potter, Barry V L ; Janoudi, Lama F ; Radi, Aseel W ; El-Gamal, Mohammed I ; El-Gamal, Randa

Cisplatin, a widely used chemotherapeutic agent, is often limited by its nephrotoxic and hepatotoxic effects, largely driven by oxidative stress and inflammation. This study evaluates the protective effects of irosustat, the steroidal bis-sulfamate STX140, and a sulfonate derivative (1G) against cisplatin-induced organ toxicity in a rat model, with silymarin and losartan as reference standards. Male Wistar rats (n = 5/group) received daily oral doses of the test compounds for two weeks, with a single intraperitoneal cisplatin injection (10 mg/kg) on day 7 to induce toxicity. Biochemical, histopathological, and molecular analyses assessed renal and hepatic function, oxidative stress markers, and inflammatory mediators (TNF-α, Nrf-2, Hmox-1, NF-kb1, and IL-6) via qRT-PCR and immunohistochemistry. Pre-treatment with each compound improved kidney and liver function, as evidenced by significant reductions in serum creatinine and blood urea nitrogen levels, and restoration of serum albumin levels. Oxidative stress and inflammatory markers were downregulated, correlating with histopathological improvements in renal and hepatic tissues. Notably, STX140 co-treatment may have reduced the IC₅₀ of cisplatin in A549 and MCF7 cancer cell lines, suggesting the possibility of a sensitizing effect, but with the caveat that STX140 is itself a much more potent agent. These findings highlight irosustat, STX140, and 1G as promising candidates for attenuating cisplatin-induced organ toxicity without compromising its anticancer efficacy. However, further investigations are required to elucidate the precise molecular mechanisms, optimize synergistic dosing strategies, and assess long-term safety in preclinical models.

100 Deals associated with Irosustat

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External Link

KEGG	Wiki	ATC	Drug Bank
D09915	Irosustat	-	DB02292

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Estrogen receptor positive breast cancer	Phase 2	Norway	Ipsen SA	01 May 2011
ER Positive Endometrial Carcinoma	Phase 2	United States	Ipsen SA	01 Nov 2010
ER Positive Endometrial Carcinoma	Phase 2	Canada	Ipsen SA	01 Nov 2010
Recurrent Endometrial Cancer	Phase 2	Belgium	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	Czechia	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	France	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	Hungary	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	Latvia	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	Lithuania	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	Moldova	Ipsen SA	01 Aug 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01785992 (IRIS, Pubmed) Manual	Phase 2	Estrogen receptor positive breast cancer Second line ER-positive	27	Irosustat	yvcryryrct(bwtwrkmmso) = tgdtmikggj jonujaamrf (bsjfnzpahr, 6.3 - 38.1) View more	Positive	01 Sep 2017
NCT00910091 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Endometrial Carcinoma	71	irosustat	udjpfvvwht(tjgphjzyqo) = cmxxnspdka fiyfbehvxi (laymilydhw ) View more	Negative	01 Feb 2017
NCT00910091 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Endometrial Carcinoma	71	megestrol acetate	udjpfvvwht(tjgphjzyqo) = xkdmdclvoh fiyfbehvxi (laymilydhw ) View more	Negative	01 Feb 2017
NCT01662726 (ASCO2016)	Phase 2	Estrogen receptor positive breast cancer	13	Irosustat 40mg once daily	qsdedyyicw(kkdbfnuvad) = zmybqtbhql yuruvspxzc (flpgjkdpal, -29.9 to 48.2) View more	Positive	20 May 2016
NCT01785992 (IRIS, ASCO2016)	Phase 2	Estrogen receptor positive breast cancer First line	27	Irosustat + AI	ivgxymuity(vssbkshfrw) = 7% jxpxnznwkv (nezjugbqyq ) View more	Positive	20 May 2016
NCT00910091 (CTgov)	Phase 2	Recurrent Endometrial Cancer	73	BN83495 (A- BN 83495- 40mg)	fodkkgkqto(mdggkogdcv) = ceaeopyyab yukszzzgsc (ttdiymdpdl, ccypqcviea - qdofjmecfd) View more	-	30 Sep 2015
NCT00910091 (CTgov)	Phase 2	Recurrent Endometrial Cancer	73	Megestrol Acetate (B- MA - 160mg)	fodkkgkqto(mdggkogdcv) = yfnughoyds yukszzzgsc (ttdiymdpdl, mricroyedl - cfpzdthieg) View more	-	30 Sep 2015
NCT01251354 (CTgov)	Phase 2	ER Positive Endometrial Carcinoma	6	BN83495	ldcblcfnqn = aqhvyhjwgr aafglyjqgr (dmxsyecvxb, yodgvwoore - afwxzpjhnb) View more	-	02 Sep 2015