Rimeporide (also known as EMD-87580) is a novel, potent and selective inhibitor of the sodium/hydrogen Na+/H+ exchanger (NHE-1) with a potential to be used as a therapeutic agent for the treatment of heart failure and for patients with Duchenne muscular dystrophy.

Physicochemical Properties

Molecular Formula	C11H15N3O5S2
Molecular Weight	333.3839
Exact Mass	333.045
Elemental Analysis	C, 39.63; H, 4.54; N, 12.60; O, 24.00; S, 19.23
CAS #	187870-78-6
Related CAS #	Rimeporide hydrochloride;187870-95-7
PubChem CID	9799487
Appearance	White to off-white solid powder
LogP	2.961
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	21
Complexity	638
Defined Atom Stereocenter Count	0
SMILES	O=C(NC(N)=N)C1=CC(S(=O)(C)=O)=C(S(=O)(C)=O)C=C1C
InChi Key	GROMEQPXDKRRIE-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H15N3O5S2/c1-6-4-8(20(2,16)17)9(21(3,18)19)5-7(6)10(15)14-11(12)13/h4-5H,1-3H3,(H4,12,13,14,15)
Chemical Name	N-(diaminomethylidene)-2-methyl-4,5-bis(methylsulfonyl)benzamide
Synonyms	EMD87580; EMD-87580; EMD 87580;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Rimeporide (EMD 87580) is a potent and selective inhibitor of the sodium-hydrogen exchanger 1 (NHE-1). [1]
ln Vitro	Rimeporide (EMD-87580) shows promise as a muscle protectant whose mode of action means it is independent of mutations. It has been demonstrated that blocking NHE-1 activity reduces intracellular Na+ and Ca2+ overload as well as pH. Rimeporide (EMD-87580) represents a new treatment option for Duchenne muscular dystrophy (DMD) [1].
ln Vivo	Rimeporide prevented inflammation and fibrosis accumulation in both skeletal muscle and heart of mdx mice, a model for Duchenne muscular dystrophy. It also had positive effects on myofibre size and oedema. In cardiomyopathic hamsters, Rimeporide prevented cardiac hypertrophy, thrombosis, and necrosis. A significant increase in overall survival was observed in treated animals, demonstrating its cardio-protective effect. [1]
Animal Protocol	In mdx mice, Rimeporide was administered to evaluate its effects on skeletal muscle and heart pathology. In cardiomyopathic hamsters, Rimeporide was administered to assess its effects on cardiac hypertrophy, thrombosis, necrosis, and overall survival. Specific details on the drug formulation, dosing frequency, route of administration, and concentration/dosage were not provided in this abstract. [1]
References	[1]. Development of Rimeporide, a sodium-hydrogen exchanger (NHE-1) inhibitor, for patients with Duchenne muscular dystrophy. Neuromuscular Disorders. October 2015 Oct 25:259-260.
Additional Infomation	Rimeporide has been used in trials studying the treatment of Muscular Dystrophy, Duchenne. Rimeporide is under development as a therapeutic agent for Duchenne muscular dystrophy (DMD). Blocking NHE-1 activity with Rimeporide decreases intracellular Na+ and Ca2+ overload and pH dysregulation, key factors in DMD pathophysiology and cardiomyopathy. Its mode of action is mutation-independent, making it potentially applicable to a broad population of DMD patients. Rimeporide has been shown to be safe and well-tolerated in Phase I trials and has been granted an Orphan Drug Designation (ODD) in Europe. A Phase Ib clinical study in patients with DMD is ongoing. It is considered an ideal complement to dystrophin-targeted therapies due to its potential to address skeletal muscle inflammation, fibrosis, and cardiomyopathy. [1]

Solubility Data

Solubility (In Vitro)

DMSO : ~20 mg/mL (~59.99 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9996 mL	14.9979 mL	29.9958 mL
	5 mM	0.5999 mL	2.9996 mL	5.9992 mL
	10 mM	0.3000 mL	1.4998 mL	2.9996 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.