Delving into the Latest Updates on Rimeporide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

NHE1

Mechanism

NHE1 inhibitors(Sodium/hydrogen exchanger 1 inhibitors)

Therapeutic Areas

Nervous System DiseasesCongenital DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication

Muscular Dystrophy, DuchenneMyotonic Dystrophy

Inactive Indication

Heart Failure

Originator Organization

Merck Serono SA

Active Organization

EspeRare FoundationMerck Serono SA

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

RegulationRare Pediatric Disease (US), Orphan Drug (EU)

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Structure

Molecular FormulaC11H15N3O5S2

InChIKeyGROMEQPXDKRRIE-UHFFFAOYSA-N

CAS Registry187870-78-6

In Duchenne Muscular Dystrophy (DMD) there is an imbalance between the levels of calcium and sodium in the muscles cells which is thought to be important in the damage which occurs overtime. Sodium/proton type 1 exchanger (NHE-1) inhibition is an innovative pathway that has proved to efficiently prevent the accumulation of muscle damage (inflammation and fibrosis) in animal models of muscular dystrophies and heart failure. Based on prior safety and efficacy results in animal and humans, NHE-1 inhibition with Rimeporide represents a new therapeutic approach with no restriction on age and on genetic subtypes which could be combined to other treatments that restore or augment dystrophin.This study examines the safety and tolerability and effects on the muscles of rimeporide, in patients aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).

Start Date01 Mar 2016

Sponsor / Collaborator

EspeRare Foundation

EUCTR2015-002530-50-FR / Not yet recruitingPhase 1IIT

A phase Ib, open label study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending oral doses of Rimeporide in patients with Duchenne Muscular Dystrophy.

Start Date18 Dec 2015

Sponsor / Collaborator

EspeRare Foundation

100 Clinical Results associated with Rimeporide

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100 Translational Medicine associated with Rimeporide

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100 Patents (Medical) associated with Rimeporide

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28

Literatures (Medical) associated with Rimeporide

27 Aug 2023·International journal of molecular sciences

Pharmacological Inhibition of NHE1 Protein Increases White Matter Resilience and Neurofunctional Recovery after Ischemic Stroke.

Article

Author: Song, Shanshan ; Sun, Dandan ; Paruchuri, Satya Siri ; Pennock, Nicholas ; Metwally, Shamseldin Ayman Hassan ; Yu, Lauren ; Capuk, Okan

To date, recanalization interventions are the only available treatments for ischemic stroke patients; however, there are no effective therapies for reducing stroke-induced neuroinflammation. We recently reported that H⁺ extrusion protein Na⁺/H⁺ exchanger-1 (NHE1) plays an important role in stroke-induced inflammation and white matter injury. In this study, we tested the efficacy of two potent NHE1 inhibitors, HOE642 and Rimeporide, with a delayed administration regimen starting at 24 h post-stroke in adult C57BL/6J mice. Post-stroke HOE642 and Rimeporide treatments accelerated motor and cognitive function recovery without affecting the initial ischemic infarct, neuronal damage, or reactive astrogliosis. However, the delayed administration of NHE1 blockers after ischemic stroke significantly reduced microglial inflammatory activation while enhanced oligodendrogenesis and white matter myelination, with an increased proliferation and decreased apoptosis of the oligodendrocytes. Our findings suggest that NHE1 protein plays an important role in microglia-mediated inflammation and white matter damage. The pharmacological blockade of NHE1 protein activity reduced microglia inflammatory responses and enhanced oligodendrogenesis and white matter repair, leading to motor and cognitive function recovery after stroke. Our study reveals the potential of targeting NHE1 protein as a therapeutic strategy for ischemic stroke therapy.

01 Jul 2022·International Journal of Biological Macromolecules

Exploring the interaction of guanidine ligands Amiloride, Rimeporide and Cariporide with DNA for understanding their role as inhibitors of Na+/H+ exchangers (NHEs): A spectroscopic and molecular docking investigation

Article

Author: Kumar, Pankaj ; Kaushik, Mahima ; Chaudhary, Swati

The inhibition of Na⁺/H⁺ Exchangers (NHEs) has shown efficacy in the pathology of several diseases like tumors, cardiovascular, and neurological disorders. The role of guanidine ligands such as amiloride, cariporide, and rimeporide as NHE inhibitors is very well documented but their interaction studies with genomic DNA are still unexplored. In this study, a combination of various biophysical and molecular docking studies was employed to investigate their binding aspects.UV-Visible, fluorescence, and circular dichroism (CD) studies indicated that guanidine ligands bind to the grooves of Calf Thymus DNA (ctDNA). Fluorescence titration studies depict that amiloride binds to ctDNA with a binding constant in the order of 10² M^-1 and free energy change (ΔG⁰) of -14.05 KJ mol^-1. Competitive fluorescence studies indicated the minor groove binding property of amiloride, whereas major groove binding mode was deduced for rimeporide and cariporide. Molecular docking studies were also found to be in accordance with the experimental results, revealing the information about the binding energy of the guanidine ligand-ctDNA complex. The docked structures depicted binding energy of -6.4 kcal mol^-1 for amiloride and - 6.6 kcal mol^-1 for rimeporide and cariporide. Such physicochemical studies of DNA-ligand interactions may facilitate the understanding of the mechanisms of NHE inhibition.

01 May 2022·Pflügers Archiv - European Journal of PhysiologyQ4 · MEDICINE

Hypotension in hereditary cardiomyopathy

Q4 · MEDICINE

Article

Author: Jacques, Danielle ; Al-Khoury, Johny ; Bkaily, Ghassan

It is well accepted that hypertension may lead to the development of heart failure (HF). However, little is known about the development of hypotension that may contribute to the onset of hereditary cardiomyopathy (HCM), thus promoting heart failure and early death. The purpose of this study is to verify whether a decrease in blood pressure takes place during different phases of HCM (asymptomatic, necrosis, hypertrophy, and heart failure). Using the well-known animal model, the UM-X7.1 hamster strain of HCM (HCMH), our results showed the absence of a change in mean arterial pressure (MAP) during the asymptomatic phase preceding the development of necrosis in HCMHs when compared to age-matched normal hamster (NH). However, there was a progressive decrease in MAP that reached its lowest level during the heart failure phase. The MAP during the development of the necrosis phase of HCM was accompanied by a significant increase in the level of the sodium-hydrogen exchanger, NHE1. Treatments with the potent NHE1 inhibitor, EMD 87580 (rimeporide), did not affect MAP of NH. However, treatments with EMD 87580 during the three phases of the development of HCM significantly reversed the hypotension associated with HCM.Our results showed that the development of HCM is associated with hypotension. These results suggest that a decrease in blood pressure could be a biomarker signal for HCM leading to HF and early death. Since the blockade of NHE1 significantly but partially prevented the reduction in MAP, this suggests that other mechanisms can contribute to the development of hypotension in HCM.

100 Deals associated with Rimeporide

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Rimeporide	-	DB12861

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Phase 2	DE	Merck Serono SA	-
Muscular Dystrophy, Duchenne	Phase 1	-	Merck Serono SA	-
Myotonic Dystrophy	Preclinical	CH	EspeRare Foundation	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02710591 (RIM4DMD, CTgov)	Phase 1	Muscular Dystrophy, Duchenne	20	Rimeporide (Cohort 1)	hlnkfpfiym(whhudypive) = bwhkbangfy xncfsthbuv (kpldbbwsra, qxnftuqqdb - kzifsztcld) View more	-	18 Jul 2019
				Rimeporide (Cohort 2)	hlnkfpfiym(whhudypive) = yhfwfcgxfb xncfsthbuv (kpldbbwsra, buexugrwiv - omajgdszsk) View more