Azumolene (EU4093 free base), an analog of Dantrolene, is a muscle relaxant. Azumolene is a ryanodine receptor (RyR) modulator and inhibits calcium release through ryanodine receptors. Azumolene may be used in malignant hyperthermia research.

Physicochemical Properties

Molecular Formula	C13H9BRN4O3
Molecular Weight	349.144
Exact Mass	347.986
Elemental Analysis	C, 44.72; H, 2.60; Br, 22.89; N, 16.05; O, 13.75
CAS #	64748-79-4
Related CAS #	64748-79-4 (free);105336-14-9 (sodium);
PubChem CID	9568620
Appearance	White to light brown solid powder
Density	1.79g/cm3
Index of Refraction	1.739
LogP	2.256
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	3
Heavy Atom Count	21
Complexity	451
Defined Atom Stereocenter Count	0
SMILES	BrC1=CC=C(C2=CN=C(/C=N/N3CC(=O)NC3=O)O2)C=C1
InChi Key	SEGCNGONCZQFDW-OMCISZLKSA-N
InChi Code	InChI=1S/C13H9BrN4O3/c14-9-3-1-8(2-4-9)10-5-15-12(21-10)6-16-18-7-11(19)17-13(18)20/h1-6H,7H2,(H,17,19,20)/b16-6+
Chemical Name	2,4-Imidazolidinedione, 1-(((5-(4-bromophenyl)-2-oxazolyl)methylene)amino)-
Synonyms	EU4093 EU-4093 EU 4093Azumolene
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

ln Vitro	Prior to the addition of caffeine and ryanodine, pretreatment with 20 µM azumolene for one to two minutes suppresses SOCE, which in turn promotes RyR-dependent sarcoplasmic reticulum Ca2+ store depletion in mouse myotubes and adult myofibers [2].
ln Vivo	The effect of Azumolene (EU4093) on twitching in intact rat soleus muscle preparations was practically maximal at a dose of 20 mg/kg. This dose of Azumolene lowered twitch amplitude to 31.9% of control values. Intrafusal muscle contraction, evaluated by spindle afferent discharge responses, is also decreased by Azumolene [1].
References	[1]. The effect of EU4093 (azumolene sodium) on the contraction of intrafusal muscle in the soleus muscle of the anaesthetized rat. Br J Pharmacol. 1989 Aug;97(4):1151-6. [2]. Accelerated activation of SOCE current in myotubes from two mouse models of anesthetic- and heat-induced sudden death. PLoS One. 2013 Oct 15;8(10):e77633.
Additional Infomation	Azumolene is a 1,3-oxazole which is substituted by a [(2,4-dioxoimidazolidin-1-yl)imino]methyl group at position 2 and a 4-bromophenyl group at position 5. It is a muscle relaxant used for the treatment/prevention of malignant hyperthermia. It has a role as a ryanodine receptor modulator and a muscle relaxant. It is a member of 1,3-oxazoles, a member of bromobenzenes and an imidazolidine-2,4-dione. It is a conjugate acid of an azumolene(1-).

Solubility Data

Solubility (In Vitro)

DMSO : ~13.89 mg/mL (~39.78 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 1.39 mg/mL (3.98 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 13.9 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: ≥ 1.39 mg/mL (3.98 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 13.9 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8642 mL	14.3209 mL	28.6418 mL
	5 mM	0.5728 mL	2.8642 mL	5.7284 mL
	10 mM	0.2864 mL	1.4321 mL	2.8642 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.