Econazole Nitrate (formerly also known as NSC-243115; SQ-13050; Spectazole) is a potent calcium channel blocker/CCB used as an imidazole-based antifungal medicine against infections caused by fungus. It was approved in 1974 for treating a variety of fungal skin infections such as athlete's foot, jock itch, and ringworm. Econazole nitrate is an effective inducer of micronuclei over a narrow dose range in cell lines V79, XEM2 and XEMd-MZ (expresses CYP1A2). Econazole nitrate inhibits the proliferation of MCF-7 cells in a time- and dose-dependent manner by MTT method and colony forming assay. Econazole nitrate results in typical characteristics of apoptosis including the morphological changes and DNA fragmentation in MCF-7 cells.

Physicochemical Properties

Molecular Formula	C18H15CL3N2O.HNO3
Molecular Weight	444.7
Exact Mass	443.02
Elemental Analysis	C, 48.62; H, 3.63; Cl, 23.92; N, 9.45; O, 14.39
CAS #	24169-02-6
Related CAS #	Econazole;27220-47-9
PubChem CID	68589
Appearance	White to off-white solid powder.
Melting Point	162°C
LogP	5.976
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	28
Complexity	404
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C(C([H])=C([H])C=1C([H])(C([H])([H])N1C([H])=NC([H])=C1[H])OC([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])Cl)Cl.O([H])[N+](=O)[O-]
InChi Key	DDXORDQKGIZAME-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H15Cl3N2O.HNO3/c19-14-3-1-13(2-4-14)11-24-18(10-23-8-7-22-12-23)16-6-5-15(20)9-17(16)21;2-1(3)4/h1-9,12,18H,10-11H2;(H,2,3,4)
Chemical Name	1-[2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl]imidazole;nitric acid
Synonyms	Econazole Nitrate; R 14,827; R 14827; Spectazole; SQ 13050; SQ13050; SQ-13050; Ecoza; epi-Pevaryl; Gyno-pevaryl; Ifenec.
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	Econazole nitrate is an effective inducer of micronuclei over a narrow dose range in cell lines V79, XEM2 and XEMd-MZ (expresses CYP1A2). Econazole nitrate inhibits the proliferation of MCF-7 cells in a time- and dose-dependent manner by MTT method and colony forming assay. Econazole nitrate results in typical characteristics of apoptosis including the morphological changes and DNA fragmentation in MCF-7 cells. Econazole nitrate results in the decrease expression of procaspase-3, procaspase-9 and bcl-2. Econazole inhibits ADP-ribose-activated currents in HEK-293 cells expressing recombinant human TRPM2 (hTRPM2). Econazole produces an essentially complete inhibition of the TRPM2-mediated current. Econazole (25-50 mM) partially inhibits capacitative Ca2+ entry induced by cyclopiazonic acid, another endoplasmic reticulum Ca2+ pump inhibitor. Econazole induces Ca2+ influx via two separate pathways: one is sensitive to La3+, the other is not. Econazole reversibly inhibits (Bu)(2)cAMP-stimulated progesterone production in a dose- and time-dependent manner in MA-10 cells without affecting total protein synthesis or P450(scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme expression or activity. Econazole is a store-operated Ca2+ channel antagonist which induces cytotoxic cell death of leukemia. Econazole (5-20 mM) arrests human colon cancer cells at the G0/G1 phase of the cell cycle. Econazole induces COLO 205 cells apoptosis evidenced by ladder formation in DNA fragmentation assay and sub-G1 peak.
ln Vivo
Animal Protocol
References	[1]. Eur J Pharmacol.2006 Feb 15;531(1-3):1-8 [2]. Iran J Pharm Res.2014 Fall;13(4):1327-34. [3]. Arzneimittelforschung, 1975. 25(2): p. 224-30. [4]. J Am Acad Dermatol. 1990 Apr;22(4):583-6.
Additional Infomation	Econazole nitrate is a white crystalline powder. (NTP, 1992) Econazole Nitrate is an imidazole derivative and broad-spectrum antimycotic agent with fungistatic properties. Econazole nitrate inhibits biosynthesis of ergosterol, thereby damaging the fungal cell wall membrane and altering its permeability which leads to a loss of essential intracellular components. In addition, econazole nitrate inhibits biosynthesis of triglycerides and phospholipids and inhibits oxidative and peroxidative enzyme activity which may contribute to cellular necrosis and cell death. Econazole nitrate is also active against some gram positive bacteria. This antifungal agent is used in the treatment various dermatomycoses. An imidazole derivative that is commonly used as a topical antifungal agent. See also: Econazole (has active moiety); Econazole nitrate; niacinamide (component of) ... View More ...

Solubility Data

Solubility (In Vitro)

DMSO : 50~89 mg/mL ( 112.44~200.13 mM ) H2O : 0.67 mg/mL (1.51 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.62 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 25.0 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: ≥ 2.5 mg/mL (5.62 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 25.0 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: ≥ 2.5 mg/mL (5.62 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (5.62 mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2487 mL	11.2435 mL	22.4871 mL
	5 mM	0.4497 mL	2.2487 mL	4.4974 mL
	10 mM	0.2249 mL	1.1244 mL	2.2487 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.