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阳性乳腺癌转移性前列腺癌+ [3]

原研机构

Ipsen SA

在研机构-

非在研机构

Ipsen SA

Peter MacCallum Cancer Institute

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-

登录后查看时间轴

结构/序列

分子式C14H15NO5S

InChIKeyDSLPMJSGSBLWRE-UHFFFAOYSA-N

CAS号288628-05-7

关联

7

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

[+6]

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

登录后查看更多信息

100 项与 Irosustat 相关的转化医学

登录后查看更多信息

100 项与 Irosustat 相关的专利（医药）

登录后查看更多信息

100

项与 Irosustat 相关的文献（医药）

2024-10-01·Steroids

Steroid sulfatase in mouse liver and testis: Characterization, ontogeny and localization

Article

作者: Balasubramonian, Barathi ; Selcer, Kyle W

Steroid hormones often circulate in the plasma as inactive sulfated forms, such as estrone sulfate and dehydroepiandrosterone sulfate. The enzyme steroid sulfatase (STS) converts these steroids into active forms, mainly estrogens, in peripheral tissues. STS is present in most tissues, but it occurs at higher levels in certain organs, notably liver and placenta. In this study, we examined the tissue distribution of STS in a prominent laboratory model, the house mouse (Mus musculus). Tissues included were heart, liver, small intestine, skeletal muscle, and gonads of both sexes. An ³H-estrone-sulfate conversion assay was used to measure STS activity in tissue homogenates and extracts. STS activities were high for hepatic tissue homogenates of both genders. Testicular STS levels were similar to those of liver, while STS activities of ovary, small intestine, heart, and muscle were considerably lower. The specific STS inhibitors, EMATE and STX-64 virtually eliminated STS activity in hepatic microsomes and cytosols, verifying that the observed enzyme activity was due to STS. Enzyme kinetic assays showed Km values of 8.6 µM for liver and 9.1 µM for testis, using E₁S as substrate. Hepatic and testicular STS activities, measured in CHAPS-extracted microsome, were low up to 5 weeks of age and were higher through 56 weeks. Western blotting, with a specific STS antibody, confirmed the presence of STS protein (65 Da) in both liver and testis. Immunofluorescence of tissue sections detected the presence of STS protein in hepatocytes, in testicular Leydig cells and in seminiferous tubules (Leydig cells and developing germ cells). These results suggest that STS may have a significant role in testicular function.

2024-10-01·Archiv der Pharmazie

An overview of the latest outlook of sulfamate derivatives as anticancer candidates (2020–2024)

Review

作者: Mustafa, Esra M. ; Anbar, Hanan S. ; El‐Gamal, Mohammed I. ; Bahaaddin, Aesheh H. ; Alajmi, Aljawhra A. ; Shahin, Afnan I. ; Hashem, Omar ; Alrashed, Aishah S.

AbstractConsidering the emergence of new anticancer drugs, in this review we emphasized and highlighted the recent reports and advances related to sulfamate‐incorporating compounds with potential anticancer activity during the last 5 years (2020–2024). Additionally, we discussed their structure–activity relationship, clarifying their potent bioactivity as anticancer agents. Sulfamate derivatives hold promise as effective therapeutic candidates against cancer. By targeting biological targets associated with the development of cancer, such as steroid sulfatases (STS), carbonic anhydrases (CAs), microtubules, NEDD8‐activating enzyme, small ubiquitin‐like modifiers (SUMO)‐activating enzyme (SAE), cyclin‐dependent kinases (CDKs), breast cancer susceptibility gene 1 (BRCA1), and so on, this can furnish small molecules as anticancer lead candidates serving the drug discovery field. For example, compound 2, an STS inhibitor, demonstrated superior activity compared to its reference, irosustat, by fivefold. In addition, compound 21, an SAE, is under phase I clinical trials. Continued research into sulfamate derivatives holds potential for the development of novel therapeutic agents targeting various diseases.

2024-01-01·Journal of Periodontal & Implant Science

Host modulation therapy for improving the osseointegration of dental implants under bone healing-suppressed conditions: a preclinical rodent-model experiment

Article

作者: Jang, Wooyoung Eric ; Park, Jin-Young ; Seo, Jeong Taeg ; Kim, Sung-Jin ; Moon, Seok Jun ; Jung, Ui-Won ; Kwon, Yoon-Hee ; Song, Young Woo

PURPOSEPlacing dental implants in areas with low bone density or in conditions where bone healing is suppressed is challenging for clinicians. An experiment using a rodent model was performed with the aim of determining the efficacy of host modulation by increasing the systemic level of cholesterol sulfate (CS) using Irosustat in the context of the bone healing process around dental implants.METHODSIn 16 ovariectomised female Sprague-Dawley rats, 2 implant fixtures were placed in the tibial bones (1 fixture on each side). At 1 week after surgery, the high-CS group (n=8) received Irosustat-mixed feed, while the control group (n=8) was fed conventionally. Block specimens were obtained at 5 weeks post-surgery for histologic analysis and the data were evaluated statistically (P<0.05).RESULTSUnlike the high-CS group, half of the specimens in the control group demonstrated severe bone resorption along with a periosteal reaction in the cortex. The mean percentages of bone-to-implant contact (21.5%) and bone density (28.1%) near the implant surface were significantly higher in the high-CS group than in the control group (P<0.05), as was the number of Haversian canals (by 5.3).CONCLUSIONSHost modulation by increasing the CS level may enhance the osseointegration of dental implants placed under conditions of impaired bone healing.

100 项与 Irosustat 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D09915	Irosustat	-	DB02292

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
复发性子宫内膜癌	临床2期	波兰	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	比利时	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	摩尔多瓦	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
复发性子宫内膜癌	临床2期	英国	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	俄罗斯	Ipsen SA	2009-08-01
复发性子宫内膜癌	临床2期	西班牙	Ipsen SA	2009-08-01
前列腺癌	临床2期	欧洲	Ipsen SA	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

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	(範襯繭蓋衊鏇顧顧構願) = 夢衊蓋網鏇餘衊遞鹹構窪鏇憲淵鹽衊顧餘鹽製 (齋範衊簾襯繭願鑰糧範, 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	(築願遞壓蓋艱餘鹹淵鏇) = 淵鬱遞願製鹽顧構願蓋廠遞願顧遞選簾鑰襯餘 (願膚鏇願艱襯簾積襯願 ) 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	(築願遞壓蓋艱餘鹹淵鏇) = 遞積顧襯淵積願願構願廠遞願顧遞選簾鑰襯餘 (願膚鏇願艱襯簾積襯願 ) 更多	不佳	2017-02-01
NCT01785992 (IRIS, ASCO2016)	临床2期	ER阳性乳腺癌一线	27	Irosustat + AI	鹹築遞廠齋鏇鏇憲願艱(願遞觸糧鏇鹹鬱鏇憲鏇) = 7% 簾壓壓憲鬱顧構鹹築餘 (衊繭獵齋醖鏇願願膚餘 ) 更多	积极	2016-05-20
NCT01662726 (ASCO2016)	临床2期	ER阳性乳腺癌	13	Irosustat 40mg once daily	積獵遞製窪選夢積淵憲(製願齋鑰衊襯艱鑰獵觸) = 窪齋鹹顧夢襯膚鑰廠壓願膚膚選積窪積鹹壓簾 (餘遞鹽鏇膚繭獵膚鏇廠, -29.9 ~ 48.2) 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)	醖餘膚範觸衊簾夢鑰夢(壓醖選鏇醖廠膚繭製壓) = 觸選夢醖觸鑰衊遞糧膚齋積糧顧糧廠選鹽壓鑰 (壓淵糧選築衊餘鬱網鬱, 鑰鏇鏇獵淵膚艱獵醖築 ~ 願淵築壓積築餘築觸簾) 更多	-	2015-09-30
NCT00910091 (CTgov)	临床2期	复发性子宫内膜癌	73	Megestrol Acetate (MA) (B- MA - 160mg)	醖餘膚範觸衊簾夢鑰夢(壓醖選鏇醖廠膚繭製壓) = 憲鹹壓積觸襯製襯獵構齋積糧顧糧廠選鹽壓鑰 (壓淵糧選築衊餘鬱網鬱, 窪遞選簾鑰憲鏇淵壓顧 ~ 鏇艱蓋積窪襯窪鹹齋鹽) 更多	-	2015-09-30
NCT01251354 (CTgov)	临床2期	ER阳性子宫内膜癌	6	BN83495	艱齋糧憲選醖遞壓鹹廠(餘鬱築襯築鑰顧繭淵壓) = 醖選餘衊衊願淵蓋窪積廠膚積膚構艱糧獵壓齋 (鹽壓範遞遞蓋糧憲膚築, 簾範廠簾憲構鏇鏇鬱積 ~ 顧糧築網積顧壓廠選襯) 更多	-	2015-09-02