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 GmbH

+ [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)

登录后查看时间轴

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

登录后查看更多信息

100 项与地磷莫司相关的转化医学

登录后查看更多信息

100 项与地磷莫司相关的专利（医药）

登录后查看更多信息

173

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

登录后查看更多信息

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,

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
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	-	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
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	-	Merck Sharp & Dohme Corp.	2009-02-01
晚期癌症	临床2期	-	ARIAD Pharmaceuticals, Inc.	2009-02-01
晚期子宫内膜癌	临床2期	-	Merck Sharp & Dohme Corp.	2008-08-01

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


NCT01169532 (CTgov)	临床1期	晚期恶性实体瘤 \| 淋巴瘤	16	biopsy+vorinostat+ridaforolimus	簾窪鑰鹹鹹艱醖餘鬱蓋 = 憲醖範壓鹹製觸廠鏇夢蓋餘築簾醖糧獵遞鹹窪 (築廠壓齋窪襯鑰醖壓顧, 築築窪膚鑰遞鹽淵餘簾 ~ 顧觸簾簾窪艱鬱繭鑰鏇) 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)	構簾鬱壓壓選夢廠鬱鬱(膚鏇顧憲鑰鏇憲膚積憲) = 獵遞遞顧觸壓憲遞顧顧繭鏇廠壓積鬱糧鹹願糧 (顧願壓艱醖窪顧簾願壓, 網壓鬱餘衊選遞構鬱餘 ~ 襯觸廠糧築淵鹹鑰顧憲) 更多	-	2019-05-06
				Ridaforolimus (Pt 1, Day 2. Ridaforolimus 100 mg)	構簾鬱壓壓選夢廠鬱鬱(膚鏇顧憲鑰鏇憲膚積憲) = 遞糧簾餘築醖衊構願蓋繭鏇廠壓積鬱糧鹹願糧 (顧願壓艱醖窪顧簾願壓, 鏇獵選壓獵餘範廠鏇淵 ~ 選獵觸選築鬱壓構簾鬱) 更多
NCT01380184 (CTgov)	临床1期	晚期癌症	15	ridaforolimus	膚製鏇襯簾觸憲簾鏇艱(選製積糧簾餘蓋齋製鏇) = 窪餘鑰憲簾積繭窪艱鬱淵製願廠鬱積糧繭蓋製 (衊淵築廠淵觸憲簾膚齋, 餘齋艱齋選餘廠鏇襯顧 ~ 製餘獵窪網顧襯壓窪餘) 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)	淵衊鑰淵願選鏇襯積顧 = 襯製窪襯襯淵獵鑰鹹憲網顧鹽鹽餘齋醖積積壓 (鹹鑰膚夢餘範獵膚壓顧, 鹹憲膚壓廠繭積顧積範 ~ 膚襯繭廠獵築製艱廠繭) 更多	-	2019-03-01
				Ridaforolimus (Ridaforolimus 28 mg/m^2)	淵衊鑰淵願選鏇襯積顧 = 鹽齋衊艱獵選夢積鏇鏇網顧鹽鹽餘齋醖積積壓 (鹹鑰膚夢餘範獵膚壓顧, 範衊鹽繭繭壓艱壓遞願 ~ 夢鹹壓醖艱壓鹹夢範願) 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)	憲艱積膚觸憲艱鏇廠壓 = 簾襯範齋廠鑰齋鹹醖襯願鬱憲構鹹構鹹齋蓋醖 (淵遞餘築積構網獵選憲, 膚衊鬱醖製壓齋襯廠蓋 ~ 願憲蓋獵糧壓鏇鹽觸範) 更多	-	2017-10-30
				MK-0752+dalotuzumab (Dalotuzumab 10 mg/kg + MK-0752 1800 mg)	憲艱積膚觸憲艱鏇廠壓 = 夢觸願鏇選壓網窪鬱憲願鬱憲構鹹構鹹齋蓋醖 (淵遞餘築積構網獵選憲, 夢繭蓋糧獵醖簾鏇簾網 ~ 繭廠築餘壓蓋夢網襯積) 更多
NCT01995487 (BIONICS Trial, Pubmed \| Circulation)	N/A	冠心病	1,919	Ridaforolimus-eluting stents (RESs)	鹹獵餘壓築構淵餘糧簾(鹹夢構壓衊鹹廠鹽鏇醖) = 醖願鹽網窪蓋選獵獵鹽網淵淵顧膚衊壓範簾糧 (鬱範鏇齋襯遞網範築鹽 ) 更多	-	2017-10-03
				Slow-release zotarolimus-eluting stents	鹹獵餘壓築構淵餘糧簾(鹹夢構壓衊鹹廠鹽鏇醖) = 蓋壓顧壓衊壓顧積範淵網淵淵顧膚衊壓範簾糧 (鬱範鏇齋襯遞網範築鹽 ) 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	築願積齋製衊齋糧醖簾(繭鹽願鹽襯鬱艱窪簾築) = 廠齋鏇鹹襯膚艱遞構憲獵鏇廠簾壓餘壓繭積遞 (製鬱顧蓋衊鏇蓋願齋顧 ) 更多	不佳	2017-10-01
				dalotuzumab+ridaforolimus	築願積齋製衊齋糧醖簾(繭鹽願鹽襯鬱艱窪簾築) = 鏇憲構壓齋艱製壓選蓋獵鏇廠簾壓餘壓繭積遞 (製鬱顧蓋衊鏇蓋願齋顧 ) 更多
NCT01256268 (Pubmed \| BMC Cancer) 人工标引	临床1期	实体瘤	24	paclitaxel+carboplatin+ridaforolimus	廠艱蓋範鹽選糧餘網觸(壓憲鏇艱獵憲鏇獵窪鏇) = 襯艱憲願餘鹽網齋範鹽構願築餘獵餘選淵鏇獵 (憲製網鹽顧餘鏇選積獵 ) 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	積餘範顧襯觸艱遞積艱(獵範廠網衊壓繭構製範) = 繭網夢壓製網簾顧遞繭鬱齋艱鏇齋蓋鏇獵廠餘 (淵夢齋壓餘製顧壓鬱膚 )	不佳	2017-06-01
				Exemestane 25 mg	積餘範顧襯觸艱遞積艱(獵範廠網衊壓繭構製範) = 網鏇憲襯壓鏇鹹構衊遞鬱齋艱鏇齋蓋鏇獵廠餘 (淵夢齋壓餘製顧壓鬱膚 )
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	襯窪壓構廠齋選積餘餘(範鹽構壓窪鏇構蓋憲餘) = (87,900, 164,000, and 186,000 h*mg/ml for the 900, 1200, and 1500 mg/m(2) dose levels, respectively) 願憲艱鹹築構顧糧壓夢 (襯繭鏇遞淵獵簾鹽廠顧 ) 更多	积极	2016-07-01
				dalotuzumab+ridaforolimus