Etoposide 33419-42-0

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Molecular Weight:

588.56 Etoposide is a semisynthetic derivative of podophyllotoxin, which inhibits DNA synthesis via topoisomerase II inhibition activity.

Biological Activity

Etoposide inhibits DNA synthesis by forming a complex with topoisomerase
II and DNA, which induces breaks in double stranded DNA and prevents
repair by topoisomerase II binding. Accumulated breaks in DNA prevent
entry into the mitotic phase of cell division, and lead to cell death.
Etoposide acts primarily in the G2 and S phases of the Cell Cycle.


Etoposide inhibits the growth of murine angiosarcoma cell line (ISOS-1)
in a 5 days-period with IC50 of 0.25 μg/mL. Cell growth of normal
murine microvascular endothelial cells (mECs) is less sensitive to
Etoposide with IC50 of 10 μg/mL). Etoposide treated for 6
hr inhibits colonies of tetraploid variant of the human leukemic
lymphoblast line CCRF-CEM with IC50 of 0.6 μM.


Etoposide
treated for 2 hr inhibits growth of human pancreatic cancer cell line
Y1, Y3, Y5, Y19, YM. YS, and YT with IC50s of 300 μg/mL, 300 μg/mL, 300
μg/mL, 91 μg/mL, 0.68 μg/mL, 300 μg/mL, 300 μg/mL, and 260 μg/mL,
respectively. Etoposide exposed for 1 hr inhibits growth
of human glioma cell lines CL5, G142, G152, G111, and G5 with IC50 of 8,
9, 9.8, 10, and 15.8 μg/mL respectively for 12 days.


Under same
condition, the IC90 value is attained in cell lines CL5, G152, G142, and
G111 at 26, 27, 32, and 33 μg/mL. Etoposide inhibition of topoisomerase
II is homogeneous for each cell. The average inhibition rates are 15%,
21.8%, 31.8%, 41.5%, and 49.5% for 1, 2, 4, 8, and 16 μg Etoposide,
respectively.


Etoposide administrated as a single agent is found to been ineffective
in many xenografts growth, such as Heterotransplanted Hepatoblastoma
NMHB1, and NMHB 2, human neuroblastoma xenograft, and human gastrointestinal cancer xenograft, while the dose of 10 mg/kg i.p.


Etoposide inhibits murine angiosarcoma cell ISOS-1 tumors in 36% of controls. Etoposide induces tumor immunity in Lewis lung cancer. A single
administration of 50 mg/kg Etoposide i.p., induces a 60% survival of
C57B1/6 mice injected with Lewis lung cancer cell (3LL) over 60 days.
About 40% of these surviving mice reject a subsequent challenge with
3LL, while none of control mice survive beyond 30 days.


3LL cells which
have survived an 90% lethal concentration of Etoposide in vitro kill 75%
of recipient mice, but 60% surviving mice reject challenge with 3LL.
Splenocytes harvested from tumor rejecting mice protect naive mice
injected with 3LL.

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Product Categories : DNA Damage > Topoisomerase Inhibitor