Delving into the Latest Updates on Ridaforolimus with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

BioNIR, Deforolimus, EluNIR

+ [8]

Target

mTORC1 x mTORC2

Mechanism

mTORC1 inhibitors(Mammalian target of Rapamycin (mTORC1) inhibitors), mTORC2 inhibitors(mTOR Complex 2 inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesOther Diseases+ [7]

Active Indication-

Inactive Indication

Advanced cancerAdvanced Endometrial CarcinomaAdvanced Sarcoma+ [27]

Originator Organization

ARIAD Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

Merck Sharp & Dohme Corp.

ARIAD Pharmaceuticals, Inc.Merck GmbH

+ [1]

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

RegulationOrphan Drug (US)

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Structure

Molecular FormulaC53H84NO14P

InChIKeyBUROJSBIWGDYCN-UHFFFAOYSA-N

CAS Registry572924-54-0

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.

Start Date14 Nov 2018

Sponsor / Collaborator

Medinol Ltd.

EUCTR2012-000335-11-DE / Not yet recruitingPhase 2

A Phase 2 Randomized Trial of the Combination of Ridaforolimusand Exemestane, Compared to Ridaforolimus, Dalotuzumaband Exemestane in High Proliferation, Estrogen Receptor PositiveBreast Cancer Patients - A phase IIb study of ridaforolimus, dalotzumab and exemestane in combination in advanced breast canc

Start Date30 Oct 2012

Sponsor / Collaborator-

100 Clinical Results associated with Ridaforolimus

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100 Translational Medicine associated with Ridaforolimus

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100 Patents (Medical) associated with Ridaforolimus

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162

Literatures (Medical) associated with Ridaforolimus

04 Sep 2024·BIOCHEMICAL JOURNAL

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

Article

Author: Hildebrand, Joanne M. ; Murphy, James 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.

01 Apr 2024·Current molecular medicine

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

Review

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

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.

16 Jan 2024·Journal of the American Heart Association

Percutaneous Coronary Interventions Using a Ridaforolimus‐Eluting Stent in Patients at High Bleeding Risk

Article

Author: Roguin, Ariel ; Karamasis, Grigoris V ; Witberg, Guy ; Jonas, Michael ; Johnson, Thomas W ; Jadhav, Sachin ; Danenberg, Haim ; Assali, Abid ; Baumbach, Andreas ; Konigstein, Maayan ; Halabi, Majdi ; Blaxill, Jonathan ; Hoole, Stephen ; Issever, Melek Ozgu ; Lev, Eli ; Vaknin-Assa, Hana ; Kerner, Arthur ; Kornowski, Ran ; Ben-Yehuda, Ori ; Segev, Amit ; Anderson, Richard

Background:

Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug‐eluting stents have been shown to be superior to bare‐metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus‐eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus‐eluting stent in patients with HBR.

Methods and Results:

This was a prospective, multicenter, binational, single‐arm, open‐label trial. Patients were defined as HBR according to the LEADERS‐FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug‐Coated Stent versus the Gazelle Bare‐Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% ( P <0.0001). Stent thrombosis (Academic Research Consortium definite and probable) occurred in 2 patients (0.6%). Bleeding Academic Research Consortium type 3 and 5 bleeding occurred in 6 patients (1.9%).

Conclusions:

We observed favorable results in patients with HBR who underwent percutaneous coronary intervention with a ridaforolimus‐eluting stent and received shortened DAPT, including a low rate of ischemic events and low rate of stent thrombosis.

Registration:

URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03877848.

4

News (Medical) associated with Ridaforolimus

25 Oct 2023

·www.nsmedicaldevices.com

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.”

Radiation Therapy

24 Oct 2023

·www.prnewswire.com

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

Radiation Therapy

31 May 2023

·www.nsmedicaldevices.com

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 Deals associated with Ridaforolimus

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External Link

KEGG	Wiki	ATC	Drug Bank
D08900	Ridaforolimus	L01XE19	DB06233

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic osteosarcoma	Phase 3	-	Merck Sharp & Dohme Corp.	01 Oct 2007
Metastatic osteosarcoma	Phase 3	-	ARIAD Pharmaceuticals, Inc.	01 Oct 2007
Metastatic Soft Tissue Sarcoma	Phase 3	-	ARIAD Pharmaceuticals, Inc.	01 Oct 2007
Metastatic Soft Tissue Sarcoma	Phase 3	-	Merck Sharp & Dohme Corp.	01 Oct 2007
Estrogen receptor positive breast cancer	Phase 2	-	Merck Sharp & Dohme Corp.	17 Sep 2010
Non-Small Cell Lung Cancer	Phase 2	-	Merck Sharp & Dohme Corp.	01 Mar 2009
Advanced cancer	Phase 2	-	ARIAD Pharmaceuticals, Inc.	01 Feb 2009
Advanced cancer	Phase 2	-	Merck Sharp & Dohme Corp.	01 Feb 2009
Castration-Resistant Prostatic Cancer	Phase 2	-	Merck Sharp & Dohme Corp.	01 Oct 2008
Castration-Resistant Prostatic Cancer	Phase 2	-	ARIAD Pharmaceuticals, Inc.	01 Oct 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01169532 (CTgov)	Phase 1	Advanced Malignant Solid Neoplasm \| Lymphoma	16	biopsy+Vorinostat+ridaforolimus	lyjbfafziv(ljvivbnhlm) = wdzfheorab mbkqwokeej (xuiewzfkht, xmymoqnwtp - cmitifbjyu) View more	-	21 Feb 2021
NCT03702608 (CTgov)	Not Applicable	Coronary Stenosis	50	EluNIR Ridaforolimus Eluting Coronary Stent System	smolmwwkfc(owmsoxwufs) = fytvuukoez srplzikxzk (mcoytwnrus, hzeodslasl - nzggvhqqjj) View more	-	28 Oct 2020
NCT00874731 (MK-8669-037 \| 8669-037, CTgov)	Phase 1	Advanced cancer	23	placebo (Pt 1, Day 1. Placebo)	snetcsoaju(ebgydaoxcf) = gknxswyahx lulxnqggfj (daomtmfjnc, cveuwhibhr - kgfhbibcrn) View more	-	06 May 2019
				Ridaforolimus (Pt 1, Day 2. Ridaforolimus 100 mg)	snetcsoaju(ebgydaoxcf) = tzvytvdupv lulxnqggfj (daomtmfjnc, tolwridxvx - okmsnjkola) View more
NCT01380184 (CTgov)	Phase 1	Advanced cancer	15	ridaforolimus	oushifkkyk(frbtzoizzj) = smeoffgbah aragfcyoeq (ojtbnqrczz, vavpdogyjy - ivflhwdfsu) View more	-	19 Apr 2019
NCT01431534 (CTgov)	Phase 1	Solid tumor \| Advanced Malignant Solid Neoplasm	20	Ridaforolimus (Ridaforolimus 22 mg/m^2)	vaoqjokbzp(yroszotxzt) = rmxeovonio brmdfejceg (zfjukrkkmc, kotdxerlrm - vlakbbyidy) View more	-	01 Mar 2019
				Ridaforolimus (Ridaforolimus 28 mg/m^2)	vaoqjokbzp(yroszotxzt) = cbqkwfxpoe brmdfejceg (zfjukrkkmc, uxukxhpxtg - qvqfyaiqbu) View more
NCT01243762 (0646-027, CTgov)	Phase 1	Advanced cancer	47	MK-0752+dalotuzumab (Dalotuzumab 7.5 mg/kg + MK-0752 1800 mg)	hiyatdtsto(klrkrpkkhm) = wxosvcrpxn lyedapwqpw (nmuqcxvpct, zdvwctdbwb - cdmcrjcyzn) View more	-	30 Oct 2017
				MK-0752+dalotuzumab (Dalotuzumab 10 mg/kg + MK-0752 1800 mg)	hiyatdtsto(klrkrpkkhm) = gnpnidjirn lyedapwqpw (nmuqcxvpct, wjxsyumtaa - ylwhcbdjvn) View more
NCT01605396 (8669-064 \| MK-8669-064, Pubmed \| Breast Cancer Res) Manual	Phase 2	Advanced breast cancer	80	dalotuzumab+ridaforolimus+exemestane	lwzksbwalm(tihfjmbiel) = wxhawgvplm opwezjcbpf (bjvnevvyth ) View more	Negative	01 Oct 2017
				dalotuzumab+ridaforolimus	lwzksbwalm(tihfjmbiel) = tuepxposcr opwezjcbpf (bjvnevvyth ) View more
NCT01256268 (Pubmed \| BMC Cancer) Manual	Phase 1	Solid tumor	24	paclitaxel+carboplatin+ridaforolimus	ksrlxvrhtm(qibygullea) = oebftpvzvu ttslckoero (ddjiqvmfvc ) View more	Positive	08 Jun 2017
NCT01234857 (8669-041, Pubmed \| Breast Cancer Res)	Phase 2	Estrogen receptor positive breast cancer	115	Ridaforolimus 30 mg + Dalotuzumab 10 mg/kg	arqcprubbx(rzejppdstz) = qtibdsnjrn pcqqafcbuc (crpjovrdsf )	Negative	01 Jun 2017
				Exemestane 25 mg	arqcprubbx(rzejppdstz) = pamdhindxx pcqqafcbuc (crpjovrdsf )
NCT01431547 (8669-062, Pubmed \| Eur J Cancer Care (Engl)) Manual	Phase 1	Solid tumor	24	dalotuzumab	emvsjfntec(ibsomjzojl) = (87,900, 164,000, and 186,000 h*mg/ml for the 900, 1200, and 1500 mg/m(2) dose levels, respectively) qomzjxvwbl (prgsqireib ) View more	Positive	01 Jul 2016
				dalotuzumab+ridaforolimus