地磷莫司(Ridaforolimus) - 药物靶点：mTORC1 x mTORC2_专利_临床

概要

基本信息

药物类型

非降解型分子胶

别名

BioNIR、Deforolimus、EluNIR

+ [8]

靶点

mTORC1 x mTORC2

作用方式

抑制剂

作用机制

mTORC1抑制剂(哺乳动物雷帕霉素靶蛋白(mTORC1)复合体抑制剂)、mTORC2抑制剂(mTOR复合物-2抑制剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病其他疾病+ [7]

在研适应症-

非在研适应症

晚期癌症晚期子宫内膜癌晚期恶性实体瘤+ [41]

原研机构

ARIAD Pharmaceuticals, Inc.

在研机构-

非在研机构

ARIAD Pharmaceuticals, Inc.

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLC

+ [1]

权益机构

Merck & Co., Inc.

ARIAD Pharmaceuticals, Inc.

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)终止

特殊审评孤儿药 (美国)

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结构/序列

分子式C53H84NO14P

InChIKeyBUROJSBIWGDYCN-UHFFFAOYSA-N

CAS号572924-54-0

关联

42

项与地磷莫司相关的临床试验

KCT0009812

/ Not yet recruitingN/AIIT

Comparison of Safety and Efficacy of Abbreviated Dual Antiplatelet Therapy in Patients with Acute Myocardial Infarction undergoing Ridaforolimus Eluting Stent EluNIR™ Implantation: A Prospective, Multicenter, Randomized Controlled Study

开始日期2024-11-01

申办/合作机构-

NCT01995500

/ Completed临床2期

BioNIR Ridaforolimus Eluting Coronary Stent System (BioNIR) EUropean Angiography Study

The NIREUS study aims to demonstrate angiographic non-inferiority for the BioNIR Ridaforolimus Eluting Coronary Stent System (hereafter referred to as BioNIR) in comparison to the Resolute zotarolimus-eluting stent (hereafter referred to as Resolute).
The trial hypothesis is that the BioNIR is non-inferior to the Resolute for the primary endpoint of angiographic in-stent late loss at 6 months.

开始日期2014-03-19

申办/合作机构

Medinol Ltd.

NCT01995487

/ CompletedN/A

BioNIR Ridaforolimus Eluting Coronary Stent System (BioNIR) In Coronary Stenosis Trial

The BioNIR study aims to show that the BioNIR ridaforolimus eluting stent is non-inferior to the Resolute zotarolimus-eluting stent for the primary clinical endpoint of target lesion failure (TLF) at 12 months; that it is non-inferior to the Resolute for the secondary endpoint of angiographic in-stent late loss at 13 months; and that it is more cost-effective.

开始日期2014-01-01

申办/合作机构

Medinol Ltd.

100 项与地磷莫司相关的临床结果

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100 项与地磷莫司相关的转化医学

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100 项与地磷莫司相关的专利（医药）

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171

项与地磷莫司相关的文献（医药）

2024-11-19·Journal of the American Heart Association

Comparison of Ridaforolimus‐Eluting and Zotarolimus‐Eluting Coronary Stents: 5‐Year Outcomes From the BIONICS and NIREUS Trials

Article

作者: Kandzari, David E. ; Stone, Gregg W. ; Love, Michael P. ; Smits, Pieter C. ; Redfors, Bjorn ; Zornitzki, Lior ; Konigstein, Maayan ; Ozan, Melek O.

Background:

The BIONICS (BioNIR Ridaforolimus‐Eluting Coronary Stent System in Coronary Stenosis) and the NIREUS (BioNIR Ridaforolimus Eluting Coronary Stent System [BioNIR] European Angiography Study) randomized clinical trials showed noninferiority of the ridaforolimus‐eluting stent (RES) compared with the zotarolimus‐eluting stent (ZES) with respect to 1‐year target‐lesion failure and 6‐month angiographic late lumen loss. We aimed to evaluate clinical outcomes between treatment groups over a 5‐year follow‐up.

Methods and Results:

Patient‐level data from the BIONICS (n=1919) and NIREUS (n=302) were pooled, comparing the outcomes of patients implanted with RES and ZES. The primary end point was the 5‐year rate of target‐lesion failure. A total of 2221 patients (63.2±10.3 years, 79.7% men) undergoing percutaneous coronary intervention with RES (n=1159) or ZES (n=1062) were included. Most clinical and angiographic characteristics were similar between groups. At 5 years, the primary end point of target‐lesion failure was similar between treatment groups (12.2% RES versus 11.3% ZES, P =0.52). Rates of TLR (7.6% RES versus 6.8% ZES, P =0.42) target‐vessel–related myocardial infarction (4.8% RES versus 4.9% ZES, P =0.95) and stent thrombosis (0.9% RES versus 0.9% ZES, P =0.87) also did not differ between groups. Target‐vessel revascularization and cardiac death were higher among the RES group (12.3% versus 9.5% P =0.037, and 3.6% versus 2.2% P =0.042, respectively). However, after correction for baseline characteristics, there was no significant difference in cardiac death between groups.

Conclusions:

In a pooled analysis of 2 randomized trials, 5‐year clinical outcomes were similar between patients undergoing percutaneous coronary intervention with RES and ZES. These results support the long‐term safety and efficacy of RES for the treatment of patients with coronary artery disease.

2024-09-04·BIOCHEMICAL JOURNAL

Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation

Article

作者: Murphy, James M. ; Hildebrand, Joanne M. ; Young, Samuel N. ; Garnish, Sarah E. ; Jacobsen, Annette V. ; Meng, Yanxiang ; Horne, Christopher R.

Necroptosis is a lytic and pro-inflammatory form of programmed cell death executed by the terminal effector, the MLKL (mixed lineage kinase domain-like) pseudokinase. Downstream of death and Toll-like receptor stimulation, MLKL is trafficked to the plasma membrane via the Golgi-, actin- and microtubule-machinery, where activated MLKL accumulates until a critical lytic threshold is exceeded and cell death ensues. Mechanistically, MLKL's lytic function relies on disengagement of the N-terminal membrane-permeabilising four-helix bundle domain from the central autoinhibitory brace helix: a process that can be experimentally mimicked by introducing the R30E MLKL mutation to induce stimulus-independent cell death. Here, we screened a library of 429 kinase inhibitors for their capacity to block R30E MLKL-mediated cell death, to identify co-effectors in the terminal steps of necroptotic signalling. We identified 13 compounds — ABT-578, AR-A014418, AZD1480, AZD5363, Idelalisib, Ipatasertib, LJI308, PHA-793887, Rapamycin, Ridaforolimus, SMI-4a, Temsirolimus and Tideglusib — each of which inhibits mammalian target of rapamycin (mTOR) signalling or regulators thereof, and blocked constitutive cell death executed by R30E MLKL. Our study implicates mTOR signalling as an auxiliary factor in promoting the transport of activated MLKL oligomers to the plasma membrane, where they accumulate into hotspots that permeabilise the lipid bilayer to cause cell death.

2024-04-01·Current molecular medicine

The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches

Review

作者: Akgul, Busra ; Zengin, Yağmur ; Ihlamur, Murat ; Abamor, Emrah Şefik ; Kelleci, Kübra ; Korkut, Şenay Vural

Abstract::

mTOR is a serine/threonine kinase that plays various roles in cell growth, proliferation, and metabolism. mTOR signaling in cancer becomes irregular. Therefore, drugs targeting mTOR have been developed. Although mTOR inhibitors rapamycin and rapamycin rapalogs (everolimus, rapamycin, temsirolimus, deforolimus, etc.) and new generation mTOR inhibitors (Rapalink, Dual PI3K/mTOR inhibitors, etc.) are used in cancer treatments, mTOR resistance mechanisms may inhibit the efficacy of these drugs. Therefore, new inhibition approaches are developed. Although these new inhibition approaches have not been widely investigated in cancer treatment, the use of nanoparticles has been evaluated as a new treatment option in a few types of cancer.

::

Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in cancer treatments, new inhibition strategies should be developed. Inhibition approaches are created using nanoparticles, and one of them offers a promising treatment option with evidence supporting its effectiveness.

5

项与地磷莫司相关的新闻（医药）

2023-10-25

·NS Medical Devices

Medinol secures FDA approval for EluNIR-PERL coronary stent system

EluNIR-PERL, the latest addition to Medinol’s EluNIR family of DES products, has four radiopaque markers, two at each end of the stent, and a radiopaque catheter tip made of hybrid polymer-metal, to facilitate superior visualisation during PCI procedures EluNIR-PERL drug-eluting coronary stent closeup. (Credit: PRNewswire/ CoSo Health) Israeli medical device maker Medinol has received the US Food and Drug Administration (FDA) approval for its EluNIR-PERL drug-eluting stent (DES) system to treat coronary artery disease. EluNIR-PERL is the latest coronary stent in its EluNIR family of DES products and builds on the company’s existing EluNIR DES system. The system comes with four radiopaque markers, two at each end of the stent, and a radiopaque catheter tip made of hybrid polymer-metal. Its unique features facilitate superior visualisation during PCI procedures including navigation through complex anatomies and placement of the stent, said the medical device maker. Medinol CEO Yoram Richter said: “We are pleased to bring technologies to the US that focus both on the benefit to patients as well as unique and meaningful advantages to surgeons, allowing for precise stent placement, shorter procedure times and reduced radiation exposure.” EluNIR-PERL is the company’s seventh-generation stent and features a unique stent design that leverages its unique CoCr framework. The CoCr framework comprises struts with varying widths and integrates radiopaque markers into the structure of the stent system. In addition, the stent also features a specialised radiopaque-enhanced metal spring tip intended for navigating through complex anatomies. The advanced design features would enable physicians with accurate positional information and precise stent placement during PCI procedures, said the medical device company. Medinol intends to commercialise the EluNIR-PERL in the US, exclusively through CoSo Health, a healthcare supply and logistics company that distributes and sells medical devices. Building on its sales rep-light model, advanced cloud-based logistics platform and customised delivery model, CoSo Health is said to reduce waste from the supply chain. CoSo Health CEO Jae Lee said: “We are proud to distribute one of the world’s best drug-eluting stents via our intuitive and easy-to-use SaaS+ platform, which reduces layers in the supply chain.”

放射疗法

2023-10-24

·PRNewswire

Medinol Receives FDA Approval for Next Generation EluNIR-PERL™ Drug-Eluting Coronary Stent System

CoSo Health to exclusively distribute Medinol's most advanced coronary DES in the U.S. DENVER and TEL AVIV, Israel, Oct. 24, 2023 /PRNewswire/ -- Medinol today announced United States Food and Drug Administration (FDA) approval for the EluNIR-PERL™ drug-eluting stent (DES) for the treatment of coronary artery disease. Continue Reading EluNIR-PERL™ Drug-Eluting Coronary Stent Closeup EluNIR-PERL builds upon the proven performance and clinical data of the EluNIR™ DES system. As the latest evolution in the EluNIR DES family, EluNIR-PERL features four radiopaque markers, two at each end of the stent, and a hybrid polymer-metal radiopaque catheter tip. These unique features allow outstanding visualization during PCI procedures whether navigating through complex anatomies or precise placement of the stent. "We are pleased to bring technologies to the U.S. that focus both on benefit to patients as well as unique and meaningful advantages to surgeons, allowing for precise stent placement, shorter procedure times and reduced radiation exposure," said Yoram Richter, CEO of Medinol. "We are proud to distribute one of the world's best drug-eluting stents via our intuitive and easy-to-use SaaS+ platform, which reduces layers in the supply chain," said Jae Lee, CEO of CoSo Health. EluNIR-PERL™ is exclusively available in the United States through CoSo Health, an innovative healthcare supply and logistics company changing the way medical devices are distributed and sold. About CoSo Health CoSo Health is redefining the healthcare supply chain with an innovative SaaS+ platform that more efficiently sources, warehouses, and distributes medical supplies and devices, bringing best-in-class products and devices to the market at great value. Visit or contact CoSo Health Chief Executive Officer Jae Lee at [email protected]. About Medinol At Medinol, we are aggressively changing paradigms in how disease states are diagnosed and treated. Whether designing cutting edge devices for stenting multiple areas of the body, dramatically reducing complications in Structural Heart procedures or providing real time insights into the physiological metrics of the human body through implantable sensors, we boldly reassess current technology and procedures and look years into the future to pioneer new devices to broaden the reach of physicians both physically and geographically. For more information, see . SOURCE CoSo Health

放射疗法

2023-05-31

·NS Medical Devices

Medinol Partners with CoSo Health to Launch the EluNIR Drug-Eluting Stent in the U.S.

CoSo Health to work with U.S. Endovascular and others to reach the U.S. market The announcement comes at a time when hospitals, payers and outpatient facilities are seeking ways to reduce surgical costs. (Credit: Medinol) CoSo Health today announced signing a U.S. distribution agreement with Medinol for EluNIR, a new generation, thin-strut drug-eluting stent (DES). Medinol is a global leader in the development of innovative implantable medical devices. U.S. Endovascular sells peripheral and coronary devices nationwide. CoSo Health is changing the way medical devices are distributed and sold. Through its sales rep-light model, innovative cloud-based logistics platform and customized delivery model, CoSo Health cuts waste from the supply chain. The announcement comes at a time when hospitals, payers and outpatient facilities are seeking ways to reduce surgical costs. “We are extremely excited to partner with CoSo Health to expand our reach within the U.S.,” said Jeff Roach, Chief Commercial Officer at Medinol. “We are both innovators – Medinol with world-class implantable device technology and CoSo Health with logistics and distribution. Together, we are disrupting the distribution of drug-eluting stents through a direct-to-end user model that brings tremendous economic value to purchasers.” The EluNIR DES offers excellent clinical outcomes and an outstanding safety profile. Its best-in-class metal-to-artery ratio and ultra-durable polymer coating, along with a unique delivery system, combine to provide a new standard in treatment capabilities. Successive generations of EluNIR are coming to the global market soon. Source: Company Press Release

100 项与地磷莫司相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08900	地磷莫司	L01XE19	DB06233

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
转移性骨肉瘤	临床3期	-	Merck Sharp & Dohme Corp.	2007-10-01
转移性骨肉瘤	临床3期	-	ARIAD Pharmaceuticals, Inc.	2007-10-01
转移性软组织肉瘤	临床3期	-	Merck Sharp & Dohme Corp.	2007-10-01
转移性软组织肉瘤	临床3期	-	ARIAD Pharmaceuticals, Inc.	2007-10-01
ER阳性乳腺癌	临床2期	-	Merck Sharp & Dohme Corp.	2010-09-17
KRAS突变非小细胞肺癌	临床2期	-	Merck Sharp & Dohme Corp.	2009-03-01
非小细胞肺癌	临床2期	-	Merck Sharp & Dohme Corp.	2009-03-01
晚期癌症	临床2期	-	ARIAD Pharmaceuticals, Inc.	2009-02-01
晚期癌症	临床2期	-	Merck Sharp & Dohme Corp.	2009-02-01
晚期子宫内膜癌	临床2期	-	Merck Sharp & Dohme Corp.	2008-08-01

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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


NCT01169532 (CTgov)	临床1期	晚期恶性实体瘤 \| 淋巴瘤	16	biopsy+vorinostat+ridaforolimus	遞夢鏇鬱窪壓鏇齋艱夢 = 範觸淵製鑰夢顧憲繭簾夢繭鹽鏇艱簾膚憲窪淵 (觸衊廠積齋築壓獵網構, 鏇構糧壓醖顧蓋壓艱構 ~ 蓋衊淵襯簾網製獵遞範) 更多	-	2021-02-21
NCT00874731 (MK-8669-037 \| 8669-037, CTgov)	临床1期	肿瘤转移 \| 晚期癌症	23	placebo (Pt 1, Day 1. Placebo)	簾觸鏇築齋鹽繭蓋憲淵(鹹窪夢齋鏇窪衊蓋糧鑰) = 顧衊醖蓋廠遞衊艱衊繭選範鹽獵膚糧顧餘範壓 (艱選繭鏇衊選衊網窪獵, 鏇構網醖簾鬱繭衊網鬱 ~ 遞鹹選壓夢淵鏇膚鑰壓) 更多	-	2019-05-06
				Ridaforolimus (Pt 1, Day 2. Ridaforolimus 100 mg)	簾觸鏇築齋鹽繭蓋憲淵(鹹窪夢齋鏇窪衊蓋糧鑰) = 夢醖鬱艱鑰積顧艱願觸選範鹽獵膚糧顧餘範壓 (艱選繭鏇衊選衊網窪獵, 構繭鬱簾遞壓憲願襯蓋 ~ 獵鬱餘艱窪膚壓簾艱築) 更多
NCT01380184 (CTgov)	临床1期	晚期癌症	15	ridaforolimus	網願鹽襯遞蓋網襯願製(蓋齋構齋蓋網夢憲夢鹹) = 憲壓壓構膚積襯積襯遞淵餘選夢蓋襯衊餘淵鑰 (鏇餘簾構遞願襯願餘鏇, 鑰願鹹願顧憲蓋膚艱衊 ~ 製願築夢壓願製觸膚衊) 更多	-	2019-04-19
NCT01431534 (CTgov)	临床1期	实体瘤 \| 晚期恶性实体瘤 \| 恶性实体肿瘤 ... 更多	20	Ridaforolimus (Ridaforolimus 22 mg/m^2)	齋簾窪衊壓壓蓋夢鹹醖 = 餘鏇鬱遞鏇範夢願遞蓋衊簾鹹壓製簾鹽餘憲顧 (鏇觸鏇憲構壓製壓淵獵, 廠遞窪獵夢衊築齋壓網 ~ 齋襯簾製獵膚壓齋構蓋) 更多	-	2019-03-01
				Ridaforolimus (Ridaforolimus 28 mg/m^2)	齋簾窪衊壓壓蓋夢鹹醖 = 簾簾鹽艱選憲憲齋鬱範衊簾鹹壓製簾鹽餘憲顧 (鏇觸鏇憲構壓製壓淵獵, 鏇壓醖膚壓製醖襯鏇積 ~ 襯顧繭夢獵膚夢積壓齋) 更多
NCT01243762 (0646-027, CTgov)	临床1期	晚期癌症	47	MK-0752+dalotuzumab (Dalotuzumab 7.5 mg/kg + MK-0752 1800 mg)	獵壓構膚糧觸餘膚醖衊 = 願獵選鹹鏇構衊繭鬱積淵糧鹽繭醖繭壓網夢醖 (廠製醖壓範製膚製窪獵, 齋鑰鏇醖衊願淵窪衊淵 ~ 簾糧鬱廠網壓夢醖齋鏇) 更多	-	2017-10-30
				MK-0752+dalotuzumab (Dalotuzumab 10 mg/kg + MK-0752 1800 mg)	獵壓構膚糧觸餘膚醖衊 = 夢憲齋鑰鏇選夢衊選鹹淵糧鹽繭醖繭壓網夢醖 (廠製醖壓範製膚製窪獵, 齋積鹽顧鹹壓蓋醖淵襯 ~ 觸願觸願築憲齋蓋糧遞) 更多
NCT01995487 (BIONICS Trial, Pubmed \| Circulation)	N/A	冠心病	1,919	Ridaforolimus-eluting stents (RESs)	鏇襯襯製窪獵觸願觸願(鏇顧鬱齋醖網範遞獵壓) = 顧餘鏇醖齋簾觸獵選鏇願觸廠顧憲範繭餘鹹積 (艱遞廠衊憲蓋蓋餘醖糧 ) 更多	-	2017-10-03
				Slow-release zotarolimus-eluting stents	鏇襯襯製窪獵觸願觸願(鏇顧鬱齋醖網範遞獵壓) = 糧繭鹹繭觸製齋醖憲網願觸廠顧憲範繭餘鹹積 (艱遞廠衊憲蓋蓋餘醖糧 ) 更多
NCT01605396 (8669-064 \| MK-8669-064, Pubmed \| Breast Cancer Res \| Breast Cancer Res Treat) 人工标引	临床2期	晚期乳腺癌	80	dalotuzumab+ridaforolimus+exemestane	鹹繭壓憲衊艱構願築鏇(糧餘製繭顧網繭構構壓) = 獵鑰顧壓構願鏇願壓遞窪鏇窪膚築鑰餘築窪鬱 (夢遞獵網鏇觸壓糧範選 ) 更多	不佳	2017-10-01
				dalotuzumab+ridaforolimus	鹹繭壓憲衊艱構願築鏇(糧餘製繭顧網繭構構壓) = 積夢選夢鹹廠衊膚願願窪鏇窪膚築鑰餘築窪鬱 (夢遞獵網鏇觸壓糧範選 ) 更多
NCT01256268 (Pubmed \| BMC Cancer) 人工标引	临床1期	实体瘤	24	paclitaxel+carboplatin+ridaforolimus	繭鏇選鏇觸製鹹願壓獵(膚壓構願積繭積繭壓艱) = 窪鬱繭鹹構糧鏇範膚製淵醖鹹齋築遞繭構襯糧 (蓋醖壓鬱廠築鏇構簾憲 ) 更多	积极	2017-06-08
NCT01234857 (Pubmed \| Breast Cancer Res Treat)	临床2期	ER阳性乳腺癌 Ki67	-	Ridaforolimus 30 mg + Dalotuzumab 10 mg/kg	窪遞窪鑰鹹衊齋憲蓋膚(廠夢範餘艱願顧衊遞獵) = 齋艱簾鹽積蓋夢艱蓋窪鹽簾遞廠糧艱獵積膚醖 (憲蓋築顧遞繭獵衊繭觸 )	不佳	2017-06-01
				Exemestane 25 mg	窪遞窪鑰鹹衊齋憲蓋膚(廠夢範餘艱願顧衊遞獵) = 壓製積築顧積憲繭鏇襯鹽簾遞廠糧艱獵積膚醖 (憲蓋築顧遞繭獵衊繭觸 )
NCT01431547 (8669-062, Pubmed \| Eur J Cancer Care (Engl) \| Eur J Cancer) 人工标引	临床1期	实体瘤	24	dalotuzumab	繭鑰鑰築齋範衊衊衊鏇(鏇廠齋餘壓膚鬱廠構襯) = (87,900, 164,000, and 186,000 h*mg/ml for the 900, 1200, and 1500 mg/m(2) dose levels, respectively) 齋築願網醖製衊壓網製 (艱構網製鑰夢製鏇鑰顧 ) 更多	积极	2016-07-01
				dalotuzumab+ridaforolimus