Chemical Name: (+)-(E)-4-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide
Appearance: White crystalline powder
Purity: ≥98.0% (HPLC)
MW: 215.21, C8H13N3O4
Storage Condition : -20ºC, protect from light and moisture
Shipping Condition : ambient temperature
Reaction of NO release
Product Description of NOR Compounds
are ideal NO donors with completely different chemical structures from
the other NO donors. Although NORs do not have any ONO2 or
ONO moiety, they spontaneously release NO at a steady rate. Even though
the NO release mechanism of NOR has not been completely determined, it
is confirmed that the byproducts do not possess any significant
bioactivities. NOR 3, isolated from Streptomyces genseosporeus, is
reported to have strong vasodilatory effects on rat and rabbit aortas
and dog coronary arteries. Its activity (ED50=1
nM) is 300 times that of isosorbide dinitrate (ISDN). NOR 3 also
increases the plasma cyclic GMP levels, whereas ISDN does not. NOR is a
potent inhibitor of platelet aggregation and thrombus formation. NOR 3
(IC50=0-7 mM) effectively inhibits 100%
of ADP-initiated human platelet Aggregation, whereas ISDN inhibits only
32% of the total aggregation, even at 100 mM concentrations. NOR 3 has
also been reported to have antianginal and cardioprotective effects in
the ischemia/reperfusion system. In the rat methacholin-induced coronary
vasospasm model, NOR 3 suppressed the elevation of the ST segment
dose-dependently and significantly at 1 mg per kg. On the other hand,
ISDN suppressed it significantly at 3.2 mg per kg. The difference in the
NO release rate of NOR reagents was reflected even on the in vivo
hypotensive effects. NOR may also be used orally in a 0.5%
methylcellulose suspension. NOR is relatively stable in DMSO solution.
NOR 1, which has the shortest half-life, is a promising reagent for
making NO standard solutions for calibration. For the preparation of the
standard solution, a precisely diluted NOR 1/DMSO solution is added to
the buffer solutions.
Nitric Oxide Release
Prepare 10 mM NOR stock solution using DMSO. Since the NOR stock
solution is not stable, keep it on an ice bath and use it in one day.
Add an appropriate volume of the NOR stock solution to the sample
solution in which NO is to be released. In order to avoid possible
damage to cells by DMSO, the volume of the NOR stock solution should not
exceed 1/50 of the sample volume. The sample solution should have
sufficient buffering action. NO will be released immediately after the
addition of the NOR stock solution.
S. Shibata, et al., Characteristics of the Vasorelaxing Action of
(3E)-4-Ethyl-2-hydroxyimino-5-nitro-3-hexamide FK409, a New Vasodilator
Isolated from Microbial Sources, in Isolated Rabbit Arteries. J Cardiovasc Pharmacol. 1991;17:508-518.2. Y. Kita, et al., Antianginal Effects of FK409, a New Spontaneous NO Releaser. Br J Pharmacol. 1994;113:1137-1140.3. Y. Kita, et al., Antiplatelet Activities of FK409, a New Spontaneous NO Releaser. Br J Pharmacol. 1994;113:385-388.4.
Y. Kita, et al., Spontaneous Nitric Oxide Release Accounts for the
Potent Pharmacological Actions of FK409. Eur J Pharmacol. 1994;257:123-130.5.
M. Hino, et al., FK409, a Novel Vasodilator Isolated from the
Acid-treated Fermentation Broth of Streptomyces Griseosporeus I.
Taxonomy, Fermentation, Isolation, and Physico-chemical and Biological Characteristics. J Antibiot. 1989; 42:1578-1583.6.
J. Decout, et al., Decomposition of FK409, a New Vasodilator:
Identification of Nitric Oxide as Metaborite. Bioorg Med Chem Lett.
1995;5:973-978.7. S. Fukuyama, et al., A New Nitric Oxide (NO) Releaser: Spontaneous NO Release from FK409. Free Radic Res. 1995;23:443-452.8. Y. Kita, et al., FR144420, a Novel, Slow, Nitric Oxide-releasing Agent. Eur J Pharmacol. 1995;275:125-130.9.
M. Kato, et al., New Reagents for Controlled Release of Nitric Oxide.
Structure-stability Relationships. Bioorg Med Chem Lett. 1996;6:33-38.10.
Y. Kita, et al., FK409, a Novel Spontaneous NO Releaser: Comparative
Pharmacological Studies with ISDN. Cardiovasc Drug Rev. 1996;14:148-165.11. Y. Hirasawa, et al., Antianginal Effects of FR144420, a Novel Nitric Oxide-releasing Agent. Eur J Pharmacol. 1996;303:55-59.12. M. Sato, et al., Nitric Oxide Raises Cytosolic Concentrations of Ca2+ in Cultured Nodose Ganglion Neurons from Rabbits. Neurosci Lett. 1996;206:69-72.13.
Y. Kita, et al., Oral Biological Activities of Spontaneous Nitric Oxide
Releaser are Accounted for by their Nitric Oxide-releaseing Rates and
Oral Absorption Manners. J Pharmacol Exp Ther. 1996;276:421-425.14.
S. Fukuyama, et al., Structure-activity Relationships of Spontaneous
Nitric Oxide Releasers, FK409 and its Derivatives. J Pharmacol Exp Ther. 1997;282:236-242.15.
Y. Kita, et al., Comparison of Hemodynamic Effects of Nitric Oxide (NO)
Donors with Different NO-releasing Properties in Rats. J Cardiovasc
Y. Hirasawa, et al., Comparison of Antiplatelet Effect of two Nitric
Oxide-donating Agents, FR146801 and FK409. Thromb Haemost. 1998;79:620-624.
How do I prepare a stock solution?
Prepare 10-50 mM NOR solution with DMSO. The DMSO should be dried. Then add enough NOR solution to the cell culture to obtain a suitable concentration of NOR.
What is the solubility of NOR compounds?
NOR 1: 100 mg per 100 ml DMSO (4.3 M)
NOR 3: 137 mg per 100 ml DMSO (6.4 M)
NOR 4: 30 mg per 100 ml DMSO (1.0 M)
NOR 5: 30 mg per 100 ml DMSO (0.9 M)
Is oral administration possible?
Yes. Please review the article by Kita and colleagues (Eur. J. Pharmacol., 257, 123-130, 1994).
How many NO molecules does each NOR molecule release in physiological conditions? What are the byproducts?
On average, each NOR molecule releases from 1 to 1.5 NO molecules in physiological conditions. Unfortunately, the structure of NOR byproducts remains unclear. However, the NOR byproducts have no cytotoxicity at the normal concentration for NO release experiments.