Dojindo,NOR 5/10/N448,NORs 是理想的 NO 供体

2022年4月28日 作者 jinpanbio

Product Description of NOR CompoundsNORs 是理想的 NO 供体,其化学结构与其他 NO 供体完全不同。尽管 NOR 没有任何 ONO2 或 ONO 部分,但它们会以稳定的速率自发释放 NO。尽管 NOR 的 NO 释放机制尚未完全确定,但已证实其副产物不具有任何显着的生物活性。据报道,从 Streptomyces genseosporeus 中分离出的 NOR 3 对大鼠和兔主动脉和狗冠状动脉具有强烈的血管舒张作用。其活性(ED50=1 nM)是硝酸异山梨酯(ISDN)的300倍。 NOR 3 也增加血浆循环 GMP 水平,而 ISDN 没有。 NOR 是血小板聚集和血栓形成的有效抑制剂。 NOR 3 (IC50=0-7 mM) 有效抑制 100% ADP 引发的人血小板聚集,而 ISDN 仅抑制总聚集的 32%,即使在 100 mM 浓度下也是如此。据报道,NOR 3 在缺血/再灌注系统中具有抗心绞痛和心脏保护作用。在大鼠乙酰甲胆碱诱导的冠状血管痉挛模型中,NOR 3 在 1 mg/kg 时剂量依赖性地显着抑制 ST 段的升高。另一方面,ISDN 将其显着抑制为每公斤 3.2 毫克。 NOR试剂的NO释放率的差异甚至反映在体内降血压作用上。 NOR 也可以在 0.5% 甲基纤维素悬浮液中口服使用。 NOR在DMSO溶液中相对稳定。 NOR 1 具有最短的半衰期,是一种很有前途的试剂,可用于制备用于校准的 NO 标准溶液。为了制备标准溶液,将精确稀释的 NOR 1/DMSO 溶液添加到缓冲溶液中。

Nitric Oxide Release1. 使用 DMSO 制备 10 mM NOR 储备溶液。 由于 NOR 原液不稳定,请将其放在冰浴上,并在一天内使用。 2. 将适量的 NOR 储备溶液添加到要释放 NO 的样品溶液中。 为避免 DMSO 可能对细胞造成损害,NOR 原液的体积不应超过样品体积的 1/50。 样品溶液应具有足够的缓冲作用。 加入 NOR 储备溶液后,NO 将立即释放。

1. 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 Pharmacol. 1997;30:223-228.16. 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?

用 DMSO 制备 10-50 mM NOR 溶液。 DMSO 应干燥。 然后向细胞培养物中加入足够的 NOR 溶液,以获得合适浓度的 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?

在生理条件下,平均每个 NOR 分子释放 1 到 1.5 个 NO 分子。 不幸的是,NOR副产物的结构仍不清楚。 然而,对于 NO 释放实验,NOR 副产物在正常浓度下没有细胞毒性。