阿非迪霉素是真核DNA復(fù)制的可逆抑制劑，可阻斷前S期的細(xì)胞周期[1]。在胚胎中產(chǎn)生對(duì)DNA復(fù)制的可逆抑制而不產(chǎn)生毒性作用所需的阿非迪霉素最低濃度為0.5 μM[2]。

體外實(shí)驗(yàn)表明，在新鮮和冷凍保存的樣品中，6 μM的阿非迪霉素在PBMC細(xì)胞中處理不會(huì)影響基線DNA損傷，但可以可靠地阻斷H2O2激發(fā)后的DNA修復(fù)[3]。在體外，在牛主動(dòng)脈內(nèi)皮細(xì)胞中用20 μM阿非迪霉素處理24小時(shí)，使其活力降低了約40%，同時(shí)NO產(chǎn)生增加，Ser1179（p-eNOS-Ser1179）處的eNOS磷酸化沒(méi)有被1,2-二（2-氨基苯氧基）乙烷-N，N，N'，N'-四乙酸四（乙酰氧基甲酯）（BAPTA-AM）（一種細(xì)胞可滲透的特異性細(xì)胞內(nèi)Ca2+螯合劑）改變[4]。此外，作為一種在體外選擇性殺死神經(jīng)母細(xì)胞癌細(xì)胞的藥劑，5 x 10（-7）M 阿非迪霉素可以殺死四種人類神經(jīng)母細(xì)胞瘤細(xì)胞系的所有細(xì)胞[5]。

體內(nèi)療效測(cè)試表明，4.5 mg 阿非迪霉素/kg體重是可作為脂質(zhì)體制劑應(yīng)用于神經(jīng)母細(xì)胞瘤（UKF-NB-3）小鼠的最大劑量[6]。阿非迪霉素（縮水甘油，具有更高的溶解劑）（100 mg/kg；腹腔注射；每3 h或9天一次）對(duì)小鼠植入的B16黑色素瘤和M5076肉瘤顯示出抗腫瘤活性，最大壽命延長(zhǎng)75% [7]。

產(chǎn)品性質(zhì)：

Cas No.：38966-21-1

別名：阿非迪霉素

化學(xué)名： (3R,4R,4aR,6aS,8R,9R,11aS,11bS)-4,9-bis(hydroxymethyl)-4,11b-dimethyltetradecahydro-8,11a-methanocyclohepta[a]naphthalene-3,9-diol

Canonical SMILES： O[C@@]1(CC[C@@]23[C@@]([H])(CC[C@]4([C@@](C)([C@@H](CC[C@@]43C)O)CO)[H])C[C@@H]1C2)CO

分子式：C20H34O4

分子量：338.48

溶解度：50mg/mL in DMSO, 10mg/mL in methanol

儲(chǔ)存條件;Store at -20°C

注意事項(xiàng)：

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References:

[1] Zhang T.Y., et al. Positive effects of treatment of donor cells with aphidicolin on the preimplantation development of somatic cell nuclear transfer embryos in Chinese Bama mini-pig (Sus Scrofa) Anim. Sci. J. 2012;83:103–110.

[2] Navarro-Serna S, et al. Effect of Aphidicolin, a Reversible Inhibitor of Eukaryotic Nuclear DNA Replication, on the Production of Genetically Modified Porcine Embryos by CRISPR/Cas9. Int J Mol Sci. 2022 Feb 15;23(4):2135.

[3] Odongo GA, et al. Optimization of the alkaline comet assay for easy repair capacity quantification of oxidative DNA damage in PBMC from human volunteers using aphidicolin block. DNA Repair (Amst). 2019 May;77:58-64.

[4] Park JH, et al. Nuclear localization of endothelial nitric oxide synthase and nitric oxide production attenuates aphidicolin-induced endothelial cell death. Nitric Oxide. 2021 May 1;109-110:12-19.

[5] Cinatl J, et al. Aphidicolin selectively kills neuroblastoma cells in vitro. Cancer Lett. 1992 Dec 24;67(2-3):199-206.

[6] Michaelis M, et al. Increased systemic efficacy of aphidicolin encapsulated in liposomes. Oncol Rep. 2005 Jan;13(1):157-60.

[7] O'Dwyer PJ, et al. Antitumor activity and biochemical effects of aphidicolin glycinate (NSC 303812) alone and in combination with cisplatin in vivo. Cancer Res. 1994 Feb 1;54(3):724-9.