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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116

Literatures (Medical) associated with Irosustat

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.

01 Aug 2025·BIOMEDICINE & PHARMACOTHERAPY

Exploring the role of estrogens and steroid sulfatase inhibition in platinum resistance, proliferation, migration, and cell death in high-grade serous ovarian cancer cells

Article

Author: Rižner, Tea Lanišnik ; Marolt, Nika ; Potter, Barry V L

The high mortality rate associated with chemoresistance in high-grade serous ovarian cancer (HGSOC) underscores the urgent need for effective treatment strategies. This study explores the role of estrogens in six HGSOC cell lines differing in carboplatin sensitivity, estrogen receptor expression, and the ability to convert estrone sulfate (E1S) into active estrogens. We assessed the effects of the steroid sulfatase (STS) inhibitor STX64 and the estrogen agonists equilin (EQ) and ethinylestradiol (EE2) on cell viability, cell death and migration, as well as their interaction with carboplatin. STX64 IC₅₀ values for cell viability varied widely-from 18.21 µM (COV362) to over 90 µM in most lines. Significant viability reductions generally occurred at ≥ 50 µM, except in Kuramochi cells that were sensitive at 10 µM, and in OVSAHO and OVCAR-4 that responded at ≥ 0.01 µM. At higher concentrations, STX64 reduced viability in all cell lines, including ERα-negative cells. Combination treatment outcomes varied: STX64 reduced carboplatin efficacy in OVSAHO and COV362 but enhanced it in Caov-3. EQ and EE2 decreased viability in several cell lines, except in OVSAHO, where EQ promoted proliferation. Both enhanced the antimigratory effects of carboplatin in cell lines with moderate ESR1:ESR2 ratios. Moreover, STX64 induced apoptosis, carboplatin triggered necrosis, and E1S potentiated both, indicating distinct cell death mechanisms. These findings emphasize the role of estrogen signaling in modulating the chemotherapy response in HGSOC. Although STX64 may not consistently enhance carboplatin effects, its strong pro-apoptotic activity and selective efficacy in ER-positive cells, highlight its promise as a potential standalone or maintenance therapy.

01 Jul 2025·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Novel nonsteroidal steroid sulfatase inhibitors containing glutamic acid unit

Article

Author: Czubak, Paweł ; Biernacki, Karol ; Demkowicz, Sebastian ; Daśko, Mateusz ; Rachon, Janusz ; Ciupak, Olga ; Martyna, Aleksandra ; Masłyk, Maciej ; Datta, Magdalena ; Kubiński, Konrad ; Rak, Janusz

In the present work, we designed and successfully synthesized novel steroid sulfatase (STS) inhibitors based on coumarin, tyramine, triazole, and flavone cores with an additional glutamic acid residue in the structure. The molecular modeling studies revealed that designed derivatives have potential to bind to the molecular target active site, at least theoretically. The biological activity of synthesized compounds was evaluated under a two-step procedure including enzymatic assay and cellular studies using human choriocarcinoma JEG-3 cells. Among the synthesized compounds, the derivative 54E was the most active in both enzymatic and cellular experiments. This result agreed with the molecular modeling data, which indicated that derivative 54E demonstrates the highest affinity to the STS active site. In the enzymatic assay, the remaining STS activity values of 12.97, 17.58, and 20.52 % were observed at 10, 1, and 0.1 μM concentrations of compound 54E, respectively. The IC₅₀ value of 22 nM determined in an experiment with JEG-3 cells for compound 54E was close to the IC₅₀ value determined for the reference STS inhibitor Irosustat (2.7 nM). During the evaluation of the uptake mechanism of the compound 54E, we found that organic anion transporting polypeptides (OATPs) may be responsible for its internalization into the cells. Furthermore, the incubation of zebrafish larvae with the compound 54E revealed no detectable toxic effects in vivo indicating that the compound 54E is a very promising candidate for further preclinical investigations.

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	United States	Ipsen SA	01 Aug 2009
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

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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	gdflrtrfue(gsgvlfhybf) = qbolrkppzm bkkuoquapy (xumkmexpfl, 6.3 - 38.1) View more	Positive	01 Sep 2017
NCT00910091 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Endometrial Carcinoma	71	irosustat	ixdojoyncw(arxdyraheo) = dydvymailp kqnukplhtv (mnyzfqdnor ) View more	Negative	01 Feb 2017
NCT00910091 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Endometrial Carcinoma	71	megestrol acetate	ixdojoyncw(arxdyraheo) = ihpvjnhlni kqnukplhtv (mnyzfqdnor ) View more	Negative	01 Feb 2017
NCT01785992 (IRIS, ASCO2016)	Phase 2	Estrogen receptor positive breast cancer First line	27	Irosustat + AI	wbmxmzkqld(nbdkhbjywf) = 7% fprwtrnexz (meubfoqjjk ) View more	Positive	20 May 2016
NCT01662726 (ASCO2016)	Phase 2	Estrogen receptor positive breast cancer	13	Irosustat 40mg once daily	olukmrdabg(edygkaxxen) = wpxaumsyar zlsholkmpm (oyxhlqnzsv, -29.9 to 48.2) View more	Positive	20 May 2016
NCT00910091 (CTgov)	Phase 2	Recurrent Endometrial Cancer	73	BN83495 (A- BN 83495- 40mg)	tqrsjcdzff(hjscnchgue) = xtscrlgjna zaxrzchagc (ikuxuaisfw, kamrahzwlt - yudovfefzb) View more	-	30 Sep 2015
NCT00910091 (CTgov)	Phase 2	Recurrent Endometrial Cancer	73	Megestrol Acetate (B- MA - 160mg)	tqrsjcdzff(hjscnchgue) = hmfkfyhcyk zaxrzchagc (ikuxuaisfw, sbragrjkot - xplxexsyxz) View more	-	30 Sep 2015
NCT01251354 (CTgov)	Phase 2	ER Positive Endometrial Carcinoma	6	BN83495	fsrgbfjpfr = cmlbvyuyoa cezcohwskp (rpentytwpw, etonpccvvs - jzdgzveqfa) View more	-	02 Sep 2015