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(+)-Aphidicolin (Synonyms: ICI 69653, NSC 234714)

Catalog No.GC10867

L'aphidicolin ((+)-Aphidicolin), un inhibiteur réversible de la réplication de l'ADN nucléaire eucaryote, peut bloquer le cycle cellulaire à la phase pré-S[1].

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(+)-Aphidicolin Chemical Structure

Cas No.: 38966-21-1

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1mg
121,00 $US
En stock
5mg
385,00 $US
En stock
25mg
1 332,00 $US
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

HeLa cells

Preparation Method

HeLa cells were synchronized by 24 h incubation with aphidicolin. After aphidicolin removal, cells were collected at different time stamps (0, 1.5, 4, 8, 12 and 24 h). DNA content was measured by flow cytometry by tracing the fluorescence intensity of cells.

Reaction Conditions

1 mg/ml; 0, 1.5, 4, 8, 12 and 24 h

Applications

Aphidicolin efficiently synchronizes HeLa cells. Late S/G2 phase was reached around 12 hours after aphidicolin removal. After 24 hours cells return to their original, unsynchronized distribution.

Animal experiment [2]:

Animal models

2-week-old WT and DKO (E2F1/E2F2 double-knockout) mice

Preparation Method

In vivo BrdU labeling and γ-H2AX accumulation in pancreases derived from 2-week-old WT and DKO mice, after i.p. injection of vehicle (saline) or aphidicolin.

Dosage form

10 µg/g; i.p.

Applications

Treatment with aphidicolin (10 µg/g) completely abolishes the incorporation of BrdU and reduces the number of cells with pan-nuclear γ-H2AX staining in DKO cells.

References:

Szczepański K, et al. Stability of cytoplasmic nanoviscosity during cell cycle of HeLa cells synchronized with Aphidicolin. Sci Rep. 2019 Nov 11;9(1):16486.
Iglesias-Ara A, et al. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution. Cell Death Differ. 2015 Oct;22(10):1577-89.

Background

L'aphidicolin ((+)-Aphidicolin), un inhibiteur réversible de la réplication de l'ADN nucléaire eucaryote, peut bloquer le cycle cellulaire à la phase pré-S[1]. La concentration minimale d'aphidicolin nécessaire pour produire une inhibition réversible de la réplication de l'ADN sans effets toxiques chez les embryons est de 0,5 µM[2].

L'expérience in vitro a montré que le traitement avec l'APC (aphidicolin) à 6 μM dans les cellules PBMC n'affectait pas les dommages à l'ADN de base, mais pouvait bloquer de manière fiable la réparation de l'ADN après un défi H2O2, tant dans des échantillons frais que cryopréservés[3]. Dans des conditions in vitro, le traitement avec 20 μM d'aphidicolin pendant 24 heures dans les cellules endothéliales aortiques bovines (BAECs) a réduit la viabilité des BAECs d'environ 40 %, ce qui s'est accompagné d'une augmentation de la production de NO, de la phosphorylation du eNOS au Ser1179 (p-eNOS-Ser1179 n'a pas été modifié par le BAPTA-AM, un chélateur spécifique et perméable aux cellules pour Ca2+ intracellulaire[4]. De plus, une concentration d'aphidicolin de 5 x 10(-7)M peut tuer toutes les cellules des quatre lignées cellulaires humaines neuroblastome en tant qu'agent qui tue sélectivement les cellules neuroblastomes in vitro [5].

Le test d'efficacité in vivo a indiqué que la dose maximale d'aphidicolin qui pouvait être appliquée sous forme de préparation liposomale et testée chez des souris porteuses de neuroblastome (UKF-NB-3) était de 4,5 mg/kg de poids corporel[6]. L'aphidicolin glycinate (un agent à solubilité plus élevée) (100 mg/kg ; i.p. ; une fois toutes les 3 heures pendant 9 jours) a montré une activité anti-tumorale contre le mélanome B16 implanté et le sarcome M5076 chez la souris, produisant des durées de vie accrues maximales de 75%[7].

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.

Chemical Properties

Cas No. 38966-21-1 SDF
Synonymes ICI 69653, NSC 234714
Chemical Name (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
Formula C20H34O4 M.Wt 338.48
Solubility 50mg/mL in DMSO, 10mg/mL in methanol Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.9544 mL 14.7719 mL 29.5438 mL
5 mM 0.5909 mL 2.9544 mL 5.9088 mL
10 mM 0.2954 mL 1.4772 mL 2.9544 mL
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