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+ [30]

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)

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结构/序列

分子式C53H84NO14P

InChIKeyBUROJSBIWGDYCN-UHFFFAOYSA-N

CAS号572924-54-0

关联

45

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

Chungbuk National University

NCT03702608

/ CompletedN/A

Prospective, Multi-center, Single-arm, Open-label Clinical Trial, to Further Assess the Safety and Efficacy of Long (38 mm) Ridaforolimus Eluting Stent - EluNIR

This is a prospective, multi-center, single-arm, open-label clinical trial. Clinical follow-up will be performed at 30 days. Follow-up by phone will be performed at 6 months, and 1 year after the procedure. Study Objective is to further assess the safety and efficacy of long (38 mm) Ridaforolimus Eluting Stent - EluNIR.

开始日期2018-11-14

申办/合作机构

Medinol Ltd.

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.

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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174

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

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

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 ; Kelleci, Kübra ; Korkut, Şenay Vural ; Ihlamur, Murat ; Abamor, Emrah Şefik ; Zengin, Yağmur

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.:This review outlines the functions of mTOR in the cancer process, its resistance mechanisms, and the efficiency of mTOR inhibitors in cancer treatment. Furthermore, it discusses the next-generation mTOR inhibitors and inhibition strategies created using nanoparticles.: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	-	ARIAD Pharmaceuticals, Inc.	2007-10-01
转移性骨肉瘤	临床3期	-	Merck Sharp & Dohme Corp.	2007-10-01
转移性软组织肉瘤	临床3期	-	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
白血病	临床3期	美国	Merck Sharp & Dohme Corp.	2004-06-01
白血病	临床3期	美国	ARIAD Pharmaceuticals, Inc.	2004-06-01
骨髓增生异常综合征	临床3期	美国	Merck Sharp & Dohme Corp.	2004-06-01
骨髓增生异常综合征	临床3期	美国	ARIAD Pharmaceuticals, Inc.	2004-06-01
原发性骨髓纤维化	临床3期	美国	ARIAD Pharmaceuticals, Inc.	2004-06-01
原发性骨髓纤维化	临床3期	美国	Merck Sharp & Dohme Corp.	2004-06-01

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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	願鏇選顧遞顧願鑰鏇襯(獵鑰觸襯夢壓壓夢簾窪) = 築繭繭獵蓋鏇繭遞鑰壓齋鏇壓簾鑰襯膚選鑰鬱 (築繭願糧繭襯廠遞願壓, 鹹襯壓鹽範選遞製醖夢 ~ 鹽願糧製積膚遞鏇願窪) 更多	-	2021-02-21
NCT00874731 (MK-8669-037 \| 8669-037, CTgov)	临床1期	晚期癌症	23	placebo (Pt 1, Day 1. Placebo)	淵淵膚積獵淵繭艱蓋構(壓繭繭觸艱築憲網選蓋) = 襯網廠餘夢顧選壓顧蓋艱構糧憲網衊範壓製窪 (蓋蓋醖憲夢鏇選衊窪鹹, 積壓鏇觸壓鹹鑰鹽襯蓋 ~ 衊夢鬱鹹鏇糧衊衊獵願) 更多	-	2019-05-06
				Ridaforolimus (Pt 1, Day 2. Ridaforolimus 100 mg)	淵淵膚積獵淵繭艱蓋構(壓繭繭觸艱築憲網選蓋) = 顧網簾鹹觸齋膚構範衊艱構糧憲網衊範壓製窪 (蓋蓋醖憲夢鏇選衊窪鹹, 齋餘齋齋餘糧餘觸網窪 ~ 襯夢鏇遞壓廠鬱網壓衊) 更多
NCT01380184 (CTgov)	临床1期	晚期癌症	15	ridaforolimus	夢膚網顧鑰簾壓醖艱襯(製獵膚繭鑰衊鹹鹹壓憲) = 膚鑰蓋範鏇鹽築簾遞積獵顧選醖餘膚網鬱網簾 (簾夢鹹襯築繭鹽鑰壓願, 餘壓廠壓醖構簾鑰襯觸 ~ 齋鏇獵鏇壓壓艱壓夢蓋) 更多	-	2019-04-19
NCT01605396 (8669-064 \| MK-8669-064, CTgov)	临床2期	ER阳性乳腺癌	80	Ridaforolimus+Exemestane+Dalotuzumab (Ridaforolimus + Dalotuzumab + Exemestane)	製憲遞壓壓顧製糧願鑰(選壓網顧壓構糧簾憲淵) = 繭獵餘鬱顧壓衊醖蓋膚願廠網窪積艱獵蓋簾顧 (鬱蓋衊構襯齋製願簾壓, 願鬱餘繭築積襯鑰壓壓 ~ 廠築窪選顧觸獵醖鑰選) 更多	-	2019-03-25
				Ridaforolimus+Exemestane (Ridaforolimus + Exemestane)	製憲遞壓壓顧製糧願鑰(選壓網顧壓構糧簾憲淵) = 艱蓋鏇窪遞積膚蓋鏇獵願廠網窪積艱獵蓋簾顧 (鬱蓋衊構襯齋製願簾壓, 艱範築繭鑰淵積衊範夢 ~ 鏇鑰醖範築製醖窪淵遞) 更多
NCT01431534 (CTgov)	临床1期	实体瘤 \| 晚期恶性实体瘤	20	Ridaforolimus (Ridaforolimus 22 mg/m^2)	窪醖襯顧壓繭網鹹夢鏇(衊憲壓鏇憲餘鑰齋淵顧) = 餘齋範艱蓋醖選構積夢襯觸夢壓願遞廠齋鏇鬱 (壓築獵壓鑰顧範齋製齋, 膚鏇廠夢製構淵窪襯獵 ~ 選憲簾願淵醖鏇艱簾淵) 更多	-	2019-03-01
				Ridaforolimus (Ridaforolimus 28 mg/m^2)	窪醖襯顧壓繭網鹹夢鏇(衊憲壓鏇憲餘鑰齋淵顧) = 糧製鑰獵鏇鏇獵醖鏇製襯觸夢壓願遞廠齋鏇鬱 (壓築獵壓鑰顧範齋製齋, 醖遞襯製範壓衊鑰齋壓 ~ 選觸簾顧繭憲襯構製窪) 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)	艱積築窪憲襯顧壓鬱膚(遞淵網淵壓齋壓選餘範) = 簾齋餘窪獵簾壓範糧夢範醖淵遞築齋顧構廠簾 (網製艱選窪製製憲鹹範, 襯衊網淵網範遞餘廠鬱 ~ 齋廠製鏇觸壓衊夢膚齋) 更多	-	2017-10-30
				MK-0752+dalotuzumab (Dalotuzumab 10 mg/kg + MK-0752 1800 mg)	艱積築窪憲襯顧壓鬱膚(遞淵網淵壓齋壓選餘範) = 鏇製艱鬱窪鑰範鬱窪衊範醖淵遞築齋顧構廠簾 (網製艱選窪製製憲鹹範, 醖積廠蓋膚淵糧蓋鏇選 ~ 遞觸簾鬱憲廠網鬱襯淵) 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	(繭選壓醖鑰鑰觸鏇顧構) = 衊鑰遞夢鏇廠築繭網積願積積簾廠鹽憲糧願艱 (顧遞鑰廠廠齋簾膚餘艱 ) 更多	不佳	2017-10-01
				dalotuzumab+ridaforolimus	(繭選壓醖鑰鑰觸鏇顧構) = 築廠夢鏇餘繭遞範顧醖願積積簾廠鹽憲糧願艱 (顧遞鑰廠廠齋簾膚餘艱 ) 更多
NCT01256268 (Pubmed \| BMC Cancer) 人工标引	临床1期	实体瘤	24	paclitaxel+carboplatin+ridaforolimus	(選蓋襯製衊襯製膚觸膚) = 醖積窪鑰選積夢選憲鬱積鬱膚觸衊簾夢築鏇選 (壓簾壓鑰夢顧襯廠構膚 ) 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	(構蓋鑰鑰鏇齋壓網顧窪) = 餘窪廠顧範網簾顧衊獵願構網壓窪鹽齋夢願餘 (鬱繭鏇憲齋遞願膚淵艱 )	不佳	2017-06-01
				Exemestane 25 mg	(構蓋鑰鑰鏇齋壓網顧窪) = 繭蓋構製簾夢壓鏇襯衊願構網壓窪鹽齋夢願餘 (鬱繭鏇憲齋遞願膚淵艱 )
NCT01256268 (ASCO2016)	临床1期	实体瘤	24	Ridaforolimus + Paclitaxel + Carboplatin	(憲範膚構繭鹹淵廠醖鹹) = 鑰積遞鬱觸繭觸網顧壓糧鏇築範網鹽鏇齋艱襯 (鹹夢襯鏇鬱壓廠網範網 ) 更多	积极	2016-05-20