[CAS NO. 38966-21-1] Aphidicolin
PRODUCTS SPECIFICATIONS [38966-21-1]
DESCRIPTION [38966-21-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 338.48 |
| Molecular Formula | C20H34O4 |
| SMILES | C[C@@]12[C@]34[C@](CC[C@@]1([H])[C@@](C)([C@H](O)CC2)CO)([H])C[C@]([C@](CO)(O)CC4)([H])C3 |
1 Publications Citing Use of MCE
Summary
Aphidicolin is an inhibitor of DNA polymerase α and δ, prevents mitotic cell division by interfering DNA polymerase activity. Aphidicolin is an antibiotic produced by mold Cephalosporium aphidicola , inhibits cellular deoxyribonucleic acid synthesis and the growth of herpes simplex virus. Aphidicolin exhibits anti-orthopoxvirus activity and potentiates apoptosis induced by arabinosyl nucleosides in a human promyelocytic leukemia cell line [1] [2] [3] .
In Vitro
Aphidicolin (0.5 μM, 5 μM; 0-5 d) selectively kills neuroblastoma cells, but shows moderate cytotoxicity on normal human embryonal cells and HeLa, H9, A549 and Caco-2 cell lines
[4]
.
Aphidicolin (0.4 μg/mL; 3 d) arrests cell cycle at G2 phase
[5]
.
Aphidicolin (100 nM-10 µM; 48 h) inhibits cell proliferation via the p53-GADD45β pathway and (1 µM; 24 h) induces apoptosis in AtT-20 cells
[6]
.
Aphidicolin (10 µM; 0-6 h) decreases the phosphorylation of Akt, (100 nM-10 µM; 24 h) increases the mRNA levels of the stress response gene growth arrest and DNA damage-inducible 45β (GADD45β), a putative downstream target of p53
[6]
.
Aphidicolin (10 µM; 0-6 h) inhibits Varicella-zoster virus (VZV) with EC
50
s of 0.5-0.6 μM, with low cytotoxicity
[7]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay [4]
| Cell Line: | NB cell lines: UKF-NB-1/2/3 and IMR-32 |
| Concentration: | 0.5 μM, 5μM |
| Incubation Time: | 1, 2, 3, 4, 5 days |
| Result: | Resulted in cellular enlargement and extension of cellular processes before cell lysis occurred. |
Cell Cycle Analysis [5]
| Cell Line: | Normal human diploid cells |
| Concentration: | 0.4 μg/mL |
| Incubation Time: | 3 days or 7 days |
| Result: |
Resulted more than 80% of the cells moved through S phase and were accumulated at G2 phase.
Inbihited the growth of the cells completely without causing apparent cell death. |
Western Blot Analysis [6]
| Cell Line: | AtT-20 cells pituitary corticotroph tumor cells |
| Concentration: | 10 µM |
| Incubation Time: | 0 min, 5 min, 30 min, 2 h, 6 h, 24 h |
| Result: |
Inhibited Akt phosphorylation in AtT-20 cells during 5 min-2 h, in a time-dependent manner.
Increased protein level of p27 during 30 min-6 h, and remarkably increased p53 level at 24 h. |
In Vivo
Aphidicolin, has been developed with higher solubility agent, namely Aphidicolin glycinate (AG; NSC 303812).
Aphidicolin glycinate (100 mg/kg; i.p.; once every 3 h; 9 d) shows anti-tumor activity against the implanted B16 melanoma and M5076 sarcoma in murine, producing maximum increased life spans of 75%
[8]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | M5076 sarcoma s.c. model or B16 melanoma i.p. model in murine [8] |
| Dosage: | 60 mg/kg, 100 mg/kg, 300 mg/kg |
| Administration: | Intraperitoneal injection; once every 3 h; 9 days |
| Result: | Inhibited tumor growth significantly. |
Appearance
Solid
Source
Cephalosporium aphidicola
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 147.72 mM ; Need ultrasonic and warming)
Stock Solutions
| Concentration Solvent Mass | 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 |
References
- [1] Dresler SL, et al. Involvement of DNA polymerase delta in DNA repair synthesis in human fibroblasts at late times after ultraviolet irradiation. Biochemistry. 1988 Aug 23;27(17):6379-83.
- [2] Bucknall RA, et al. Antiviral effects of aphidicolin, a new antibiotic produced by Cephalosporium aphidicola. Antimicrob Agents Chemother. 1973 Sep;4(3):294-8.
- [3] Kuwakado K, et al. Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human myeloid leukemiacell lines. Biochem Pharmacol. 1993 Dec 3;46(11):1909-16.
- [4] Cinatl J, et al. Aphidicolin selectively kills neuroblastoma cells in vitro. Cancer Lett. 1992 Dec 24;67(2-3):199-206.
- [5] Kageyama K, et al. Aphidicolin inhibits cell proliferation via the p53-GADD45β pathway in AtT-20 cells. Endocr J. 2015;62(7):645-54.
- [6] Fukuda M, Ohashi M. Aphidicolin inhibits cell growth by accumulation of G2 cells. Cell Biol Int Rep. 1983 Aug;7(8):579-85.
- [7] Rowe J, et al. Compounds that target host cell proteins prevent varicella-zoster virus replication in culture, ex vivo, and in SCID-Hu mice. Antiviral Res. 2010 Jun;86(3):276-85.
- [8] 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.
Synonyms