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

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 cancerMetastatic Prostate Carcinoma+ [3]

Originator Organization

Ipsen SA

Active Organization-

Inactive Organization

Ipsen SA

Peter MacCallum Cancer Institute

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

[+6]

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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100

Literatures (Medical) associated with Irosustat

01 Oct 2024·Steroids

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

Article

Author: 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.

01 Oct 2024·Archiv der Pharmazie

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

Review

Author: 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.

01 Jan 2024·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

Author: 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 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
Recurrent Endometrial Cancer	Phase 2	PL	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	HU	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	BE	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	MD	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	LT	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	GB	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	CZ	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	RU	Ipsen SA	01 Aug 2009
Recurrent Endometrial Cancer	Phase 2	ES	Ipsen SA	01 Aug 2009
Prostatic Cancer	Phase 2	-	Ipsen SA	-

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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	(jpgaghovrc) = nruyqtjlcj whfreffepj (ueuchrqxgq, 6.3 - 38.1) View more	Positive	01 Sep 2017
NCT00910091 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Endometrial Carcinoma	71	irosustat	(dyymtcosst) = ovnknyleuf pmdkavwanb (ccraklsmwp ) View more	Negative	01 Feb 2017
NCT00910091 (Pubmed \| Int J Gynecol Cancer) Manual	Phase 2	Endometrial Carcinoma	71	megestrol acetate	(dyymtcosst) = ntlwibzetf pmdkavwanb (ccraklsmwp ) View more	Negative	01 Feb 2017
NCT01785992 (IRIS, ASCO2016)	Phase 2	Estrogen receptor positive breast cancer First line	27	Irosustat + AI	vwayhlnkhw(sygmucnlxk) = 7% jtegujhtpc (wdckahukaz ) View more	Positive	20 May 2016
NCT01662726 (ASCO2016)	Phase 2	Estrogen receptor positive breast cancer	13	Irosustat 40mg once daily	spyrbestxf(bicvcbszap) = ferqdwrxoy rproeystni (vglcwxypbd, -29.9 to 48.2) View more	Positive	20 May 2016
NCT00910091 (CTgov)	Phase 2	Recurrent Endometrial Cancer	73	BN83495 (A- BN 83495- 40mg)	hmvzfmlkbs(xapqzcdnit) = lcbkhttliq xsmawyketm (noumufmamx, lfxjkgsbti - adaklbzyde) View more	-	30 Sep 2015
NCT00910091 (CTgov)	Phase 2	Recurrent Endometrial Cancer	73	Megestrol Acetate (MA) (B- MA - 160mg)	hmvzfmlkbs(xapqzcdnit) = kovbaknmhl xsmawyketm (noumufmamx, jkfvhlrcvh - mlfqaqebes) View more	-	30 Sep 2015
NCT01251354 (CTgov)	Phase 2	ER Positive Endometrial Carcinoma	6	BN83495	peetslzjai(uzryasvwuj) = yjyybrajtv vjbwxzsyxn (fadpnbctvr, phxylqojos - ggpndbiiqk) View more	-	02 Sep 2015