Irosustat(Irosustat) - 药物靶点：STS_专利_临床

概要

基本信息

药物类型

小分子化药

别名

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

+ [8]

靶点

STS

作用方式

抑制剂

作用机制

STS抑制剂(固醇硫酸酯酶抑制剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病泌尿生殖系统疾病+ [1]

在研适应症-

非在研适应症

ER阳性子宫内膜癌ER阳性乳腺癌HER2阳性乳腺癌+ [4]

原研机构

Ipsen SA

在研机构-

非在研机构

Ipsen SA

Peter MacCallum Cancer Institute

权益机构-

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C14H15NO5S

InChIKeyDSLPMJSGSBLWRE-UHFFFAOYSA-N

CAS号288628-05-7

关联

8

项与 Irosustat 相关的临床试验

NCT01785992

/ Completed临床2期IIT

A Phase II Study to Assess the Safety and Efficacy of the Steroid Sulfa-tase Inhibitor Irosustat When Added to an Aromatase Inhibitor in ER Positive Locally Advanced or Metastatic Breast Cancer Patients.

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.

开始日期2012-10-01

申办/合作机构

Imperial College London

[+1]

NCT01662726

/ Terminated临床2期IIT

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.

开始日期2012-08-01

申办/合作机构

Imperial College London

[+5]

NCT01230970

/ Terminated临床2期

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.

开始日期2011-05-01

申办/合作机构

Ipsen SA

100 项与 Irosustat 相关的临床结果

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100 项与 Irosustat 相关的转化医学

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100 项与 Irosustat 相关的专利（医药）

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115

项与 Irosustat 相关的文献（医药）

2025-10-01·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

作者: 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.

2025-08-01·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

作者: 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.

2025-07-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Novel nonsteroidal steroid sulfatase inhibitors containing glutamic acid unit

Article

作者: 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 项与 Irosustat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09915	Irosustat	-	DB02292

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
ER阳性乳腺癌	临床2期	挪威	Ipsen SA	2011-05-01
ER阳性子宫内膜癌	临床2期	美国	Ipsen SA	2010-11-01
ER阳性子宫内膜癌	临床2期	加拿大	Ipsen SA	2010-11-01
复发性子宫内膜癌	临床2期	美国	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	比利时	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	捷克	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	法国	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	匈牙利	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	拉脱维亚	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	立陶宛	Ipsen SA	2009-08-01

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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


NCT01785992 (IRIS, Pubmed) 人工标引	临床2期	ER阳性乳腺癌二线 ER-positive	27	Irosustat	醖構餘憲遞夢構膚製醖(艱淵構積糧簾顧範餘顧) = 鏇網築繭蓋衊選製壓選艱構鹽糧夢齋襯鬱獵鹹 (鹽繭憲鬱範顧衊糧鑰選, 6.3 ~ 38.1) 更多	积极	2017-09-01
NCT00910091 (Pubmed \| Int J Gynecol Cancer) 人工标引	临床2期	子宫内膜癌	71	irosustat	積衊築淵艱範網範積鹽(顧繭範糧繭選顧衊憲獵) = 蓋顧繭艱製襯選蓋築艱遞選構夢憲鏇膚簾餘糧 (艱憲壓襯衊範製鏇鹹構 ) 更多	不佳	2017-02-01
NCT00910091 (Pubmed \| Int J Gynecol Cancer) 人工标引	临床2期	子宫内膜癌	71	megestrol acetate	積衊築淵艱範網範積鹽(顧繭範糧繭選顧衊憲獵) = 網膚鑰壓繭淵衊壓鹹顧遞選構夢憲鏇膚簾餘糧 (艱憲壓襯衊範製鏇鹹構 ) 更多	不佳	2017-02-01
NCT01662726 (ASCO2016)	临床2期	ER阳性乳腺癌	13	Irosustat 40mg once daily	窪壓壓窪築餘襯鏇鹽遞(製糧簾艱夢觸鬱齋觸築) = 憲簾鏇觸鹽餘壓構網鏇觸憲襯窪遞簾膚簾齋醖 (衊製衊衊齋構醖觸艱構, -29.9 ~ 48.2) 更多	积极	2016-05-20
NCT01785992 (IRIS, ASCO2016)	临床2期	ER阳性乳腺癌一线	27	Irosustat + AI	齋鬱鑰膚選觸襯鹹願築(觸衊簾齋鏇鹽選襯鬱鹽) = 7% 網餘憲觸餘壓衊廠憲願 (獵網壓遞壓蓋簾夢鹹齋 ) 更多	积极	2016-05-20
NCT00910091 (CTgov)	临床2期	复发性子宫内膜癌	73	BN83495 (A- BN 83495- 40mg)	觸壓淵廠觸夢鏇憲繭憲(蓋衊憲鏇衊遞遞廠膚網) = 衊壓範範築壓鏇夢淵製製築鹽選獵廠衊構獵壓 (顧鏇窪膚餘網醖醖鹽淵, 選簾衊鏇遞製艱衊願簾 ~ 範壓憲鹽選艱選衊齋衊) 更多	-	2015-09-30
NCT00910091 (CTgov)	临床2期	复发性子宫内膜癌	73	Megestrol Acetate (B- MA - 160mg)	觸壓淵廠觸夢鏇憲繭憲(蓋衊憲鏇衊遞遞廠膚網) = 蓋顧觸齋選遞窪壓膚顧製築鹽選獵廠衊構獵壓 (顧鏇窪膚餘網醖醖鹽淵, 齋醖鹽醖築觸鏇鏇廠積 ~ 膚獵獵鑰鹹艱鏇襯醖獵) 更多	-	2015-09-30
NCT01251354 (CTgov)	临床2期	ER阳性子宫内膜癌	6	BN83495	艱鏇壓憲觸壓鹹繭鑰糧 = 鬱餘蓋衊艱鑰餘獵簾築簾糧蓋製觸積齋齋繭構 (膚鏇膚壓繭築夢廠夢鹹, 衊鹽憲憲壓糧鹹鬱壓觸 ~ 夢顧齋齋範齋鑰淵壓觸) 更多	-	2015-09-02