Etoposide phosphate, 磷酸依托泊苷

Topoisomerase II inhibitor. Forms ternary complex with DNA and topoisomerase II to prevent re-ligation of DNA strands. Causes errors in DNA synthesis and apoptosis in cancer cells. Increases acetylation of eEF1A. Antitumor agent. Active in vivo and in vitro.

Etoposide Phosphate is a phosphate salt of a semisynthetic derivative of podophyllotoxin. Etoposide binds to the enzyme topoisomerase II, inducing double-strand DNA breaks, inhibiting DNA repair, and resulting in decreased DNA synthesis and tumor cell proliferation. Cells in the S and G2 phases of the cell cycle are most sensitive to this agent. (NCI04)

Etoposide phosphate is a furonaphthodioxole.

Title: Etoposide

CAS Registry Number: 122332-48-3

CAS Name: 9-[(4,6-O-Ethylidene-b-D-glucopyranosyl)oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3¢,4¢:6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one

Additional Names: 4'-demethylepipodophyllotoxin 9-[4,6-O-ethylidene-b-D-glucopyranoside]; EPEG

Manufacturers' Codes: NSC-141540; VP-16-213

Trademarks: Lastet (Nippon Kayaku); Vepesid (BMS)

Molecular Formula: C29H32O13

Molecular Weight: 588.56

Percent Composition: C 59.18%, H 5.48%, O 35.34%

Literature References: DNA topoisomerase II inhibitor. Semi-synthetic deriv of podophyllotoxin, related structurally to teniposide, q.q.v. Prepn: C. Keller-Juslén et al., US 3524844 (1970 to Sandoz); idem et al., J. Med. Chem. 14, 936 (1971). Teratogenicity and cytogenicity study: S. M. Sieber et al., Teratology 18, 31 (1978). Review of pharmacokinetics and assay methods: P. I. Clark, M. L. Slevin, Clin. Pharmacokinet. 12, 223-252 (1987). Comprehensive description: J. J. M. Holthuis et al., Anal. Profiles Drug Subs. 18, 121-151 (1989). Review of pharmacology and clinical experience: J. D. Hainsworth, F. A. Greco, Ann. Oncol. 6, 325-341 (1995); S. Joel, Cancer Treat. Rev. 22, 179-221 (1996).

Properties: Crystals from methanol, mp 236-251°. [a]D20 -110.5° (c = 0.6 in chloroform). uv max (abs methanol): 283 nm (e 4245). pKa 9.8. Very sol in methanol, chloroform; slightly sol in ethanol; sparingly sol in water.

Melting point: mp 236-251°

pKa: pKa 9.8

Optical Rotation: [a]D20 -110.5° (c = 0.6 in chloroform)

Absorption maximum: uv max (abs methanol): 283 nm (e 4245)

Derivative Type: Phosphate

CAS Registry Number: 117091-64-2

Manufacturers' Codes: BMY-40481

Trademarks: Etopophos (BMS)

Molecular Formula: C29H33O16P

Molecular Weight: 668.54

Percent Composition: C 52.10%, H 4.98%, O 38.29%, P 4.63%

Literature References: Review: A. H. I. Witterland et al., Pharm. World Sci. 18, 163-170 (1996).

Properties: Sol in water. Practically insol in organic solvents.

 Therap-Cat: Antineoplastic.

Keywords: Antineoplastic; Alkaloids/Natural Products; Podophyllum Derivatives; Topoisomerase II Inhibitor.

COA:

Product name:  Etoposide phosphate                M.F.: C₂₉H₃₃O₁₆P

M.W._: 668.5                                                   CAS: 117091-64-2 or 122332-48-3