A1971-100mg | Etoposide [33419-42-0] Quimigen Portugal

Background

Etoposide (VP-16) is the first agent recognized as a topoisomerase II inhibitor of anticancer drug with IC50 of 59.2 μM.

The activity of the topoisomerase II enzyme on re-ligation of DNA strands is interrupted by etoposide. A ternary complex with DNA is formed by etoposide, and causes DNA strands to break [1]. The enzyme was more important in cancer cell than healthy cells, because cancer cells divided more rapidly. So etoposide induced apoptosis of the cancer cells [2]. Etoposide exhibited cytotoxic activity against HepG2 and MOLT-3 cancer cells with IC50 of 30.16 μM and 0.051μM [3]. The IC50 values of etoposide against the tumor cell lines of BGC-823, HeLa, and A549 were 43.74 ± 5.13, 209.90 ± 13.42, and 139.54 ± 7.05 μM, respectively [4].

References:
[1] Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010 May 28; 17 (5): 421-33.
[2] Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004 Sep 15; 44 (4): 441-59.
[3] Pingaew R, Mandi P, Nantasenamat C, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity. Eur J Med Chem. 2014 May 6; 81C: 192-203.
[4] Xiao L, Zhao W, Li HM, Wan DJ, Li DS, Chen T, Tang YJ. Design and synthesis of the novel DNA topoisomerase II inhibitors: Esterification and amination substituted 4'-demethylepipodophyllotoxin derivates exhibiting anti-tumor activity by activating ATM/ATR signaling pathways. Eur J Med Chem. 2014 Jun 10; 80: 267-77.

Product Citation

1. Phoebe McCrorie, Jatin Mistry, et al. "Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours." Eur J Pharm Biopharm. 2020 Oct 14;S0939-6411(20)30305-2. PMID:33068736
2. Cai B, Hu Z, et al. "Triptolide impairs genome integrity by directly blocking the enzymatic activity of DNA-PKcs in human cells." Biomed Pharmacother. 2020;129:110427. PMID:32574974
3. Zhao K, Wang X, et al. "A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers." PLoS Biol. 2020;18(3):e3000666. PMID:32203529
4. Wang Z, Chen J, et al. "cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity." J Clin Invest. 2019 Aug 13;130:4850-4862. PMID:31408442
5. Barot S, Abo-Ali EM, et al. "Inhibition of glycogen catabolism induces intrinsic apoptosis and augments multikinase inhibitors in hepatocellular carcinoma cells." Exp Cell Res. 2019 Aug 15;381(2):288-300. PMID:31128107
6. Rogers C, Erkes DA, et al. "Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation." Nat Commun. 2019 Apr 11;10(1):1689. PMID:30976076
7. Wu Q, Wei X, et al. "Bionic 3D spheroids biosensor chips for high-throughput and dynamic drug screening." Biomed Microdevices. 2018 Sep 15;20(4):82. PMID:30220069
8. Lochmann TL, Floros KV, et al. "Venetoclax Is Effective in Small-Cell Lung Cancers with High BCL-2 Expression." Clin Cancer Res. 2018 Jan 15;24(2):360-369. PMID:29118061
9. Xia L, Xiao X, et al. "Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGFβ signaling." Oncogene. 2018 Jan 18;37(3):323-331. PMID:28925397

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Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	588.56
Cas No.	33419-42-0
Formula	C₂₉H₃₂O₁₃
Solubility	≥29.45 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
Chemical Name	(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
SDF	Download SDF
Canonical SMILES	CC1OCC2C(O1)C(C(C(O2)OC3C4COC(=O)C4C(C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Kinase experiment [1]:
Topoisomerase II activity assay	Nuclear extracts are prepared, and nuclei are isolated. The activity of topoisomerase II is calculated from the percentage of decatenation obtained. Tritiated kinoplast DNA (KDNA 0.22 μg) is used as a substrate. Etoposide and topoisomerase II are incubated for 30 min at 37°C and are stopped with 1% sodium dodecyl sulfate (SDS) and proteinase K (100 μg/mL). The percentages of decatenation and inhibition of topoisomerase II by Etoposide are obtained.
Cell experiment [2]:
Cell lines	BGC-823, HeLa and A549 cells
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.
Reaction Conditions	0.5, 1, 10, 20, 50, 100, 200 and 500 μM; 2 d
Applications	The IC50 values of Etoposide against the tumor cell lines of BGC-823, HeLa and A549 were 43.74 ± 5.13 μM, 209.90 ± 13.42 μM and 139.54 ± 7.05 μM, respectively.
Animal experiment [3]:
Animal models	Murine angiosarcoma xenografts ISOS-1
Dosage form	2.5, 5, 10 mg/kg; i.p.; every day for 5 days
Applications	The dose of 10 mg/kg Etoposide (i.p.) inhibited murine angiosarcoma cell ISOS-1 tumors.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Beauchesne P, Bertrand S, N'guyen MJ, Christianson T, Dore JF, Mornex F, Bonner JA. Etoposide sensitivity of radioresistant human glioma cell lines. Cancer Chemother Pharmacol. 1998; 41 (2): 93-7. [2] Xiao L, Zhao W, Li HM, Wan DJ, Li DS, Chen T, Tang YJ. Design and synthesis of the novel DNA topoisomerase II inhibitors: Esterification and amination substituted 4'-demethylepipodophyllotoxin derivates exhibiting anti-tumor activity by activating ATM/ATR signaling pathways. Eur J Med Chem. 2014 Jun 10; 80: 267-77. [3] Ma G1, Masuzawa M, Hamada Y, Haraguchi F, Tamauchi H, Sakurai Y, Fujimura T, Katsuoka K. Treatment of murine angiosarcoma with etoposide, TNP-470 and prednisolone. J Dermatol Sci. 2000 Nov; 24 (2): 126-33.