U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry EPIMERIC
Molecular Formula C36H42O17
Molecular Weight 746.7085
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 11
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ETOPOSIDE TONIRIBATE

SMILES

[H][C@]12COC(=O)[C@]1([H])[C@H](C3=CC(OC)=C(OC(=O)OCC4COC(C)(C)O4)C(OC)=C3)C5=C(C=C6OCOC6=C5)[C@H]2O[C@@H]7O[C@]8([H])CO[C@@H](C)O[C@@]8([H])[C@H](O)[C@H]7O

InChI

InChIKey=FCWSQAKOPTZCOD-SQYSSJHTSA-N
InChI=1S/C36H42O17/c1-15-43-13-25-32(49-15)28(37)29(38)34(50-25)51-30-19-9-22-21(46-14-47-22)8-18(19)26(27-20(30)12-44-33(27)39)16-6-23(41-4)31(24(7-16)42-5)52-35(40)45-10-17-11-48-36(2,3)53-17/h6-9,15,17,20,25-30,32,34,37-38H,10-14H2,1-5H3/t15-,17?,20+,25-,26-,27+,28-,29-,30-,32-,34+/m1/s1

HIDE SMILES / InChI
Molecular Formula C36H42O17
Molecular Weight 746.7085
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 10 / 11
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020457s013lbl.pdf

Etoposide (trade name Etopophos) is a semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. It has been in clinical use for more than two decades and remains one of the most highly prescribed anticancer drugs in the world. The primary cytotoxic target for etoposide is topoisomerase II. This ubiquitous enzyme regulates DNA under- and over winding, and removes knots and tangles from the genome by generating transient double-stranded breaks in the double helix. Etoposide kills cells by stabilizing a covalent enzyme-cleaved DNA complex (known as the cleavage complex) that is a transient intermediate in the catalytic cycle of topoisomerase II. The accumulation of cleavage complexes in treated cells leads to the generation of permanent DNA strand breaks, which trigger recombination/repair pathways, mutagenesis, and chromosomal translocations. If these breaks overwhelm the cell, they can initiate death pathways. Thus, etoposide converts topoisomerase II from an essential enzyme to a potent cellular toxin that fragments the genome. Although the topoisomerase II-DNA cleavage complex is an important target for cancer chemotherapy, there also is evidence that topoisomerase II-mediated DNA strand breaks induced by etoposide and other agents can trigger chromosomal translocations that lead to specific types of leukemia. Etopophos (etoposide phosphate) is indicated in the management of the following neoplasms: Refractory Testicular Tumors-and for Small Cell Lung Cancer. The in vitro cytotoxicity observed for etoposide phosphate is significantly less than that seen with etoposide, which is believed due to the necessity for conversion in vivo to the active moiety, etoposide, by dephosphorylation. The mechanism of action is believed to be the same as that of etoposide.

CNS Activity

Approval Year

1983
81
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.8 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
ETOPOPHOS PRESERVATIVE FREE

Approved Use

ETOPOPHOS for Injection is indicated in the management of the following neoplasms: Refractory Testicular Tumors-ETOPOPHOS for Injection in combination therapy with other approved chemotherapeutic agents in patients with refractory testicular tumors who have already received appropriate surgical, chemotherapeutic, and radiotherapeutic therapy. Small Cell Lung Cancer-ETOPOPHOS for Injection in combination with other approved chemotherapeutic agents as first-line treatment in patients with small cell lung cancer.

Launch Date

4.37270413E11
Primary
Approved
8429
ETOPOPHOS PRESERVATIVE FREE

Approved Use

ETOPOPHOS for Injection is indicated in the management of the following neoplasms: Refractory Testicular Tumors-ETOPOPHOS for Injection in combination therapy with other approved chemotherapeutic agents in patients with refractory testicular tumors who have already received appropriate surgical, chemotherapeutic, and radiotherapeutic therapy. Small Cell Lung Cancer-ETOPOPHOS for Injection in combination with other approved chemotherapeutic agents as first-line treatment in patients with small cell lung cancer.

Launch Date

8.3229121E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
14.7 μg/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8431968
80 mg/m² other, intravenous
dose: 80 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
ETOPOSIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
18.66 μg/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8431968
95 mg/m² other, intravenous
dose: 95 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
ETOPOSIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2707 μg × min/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8431968
80 mg/m² other, intravenous
dose: 80 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
ETOPOSIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
5806 μg × min/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8431968
95 mg/m² other, intravenous
dose: 95 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
ETOPOSIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.37 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8431968
80 mg/m² other, intravenous
dose: 80 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
ETOPOSIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.32 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/8431968
95 mg/m² other, intravenous
dose: 95 mg/m²
route of administration: Intravenous
experiment type: OTHER
co-administered:
ETOPOSIDE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/019557s028lbl.pdf
ETOPOSIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
25 mg/m2 3 times / day multiple, oral
Highest studied dose
Dose: 25 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 25 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
DLT: Neutropenia, Thrombocytopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 25%)
Thrombocytopenia (grade 4, 12.5%)
Leukopenia (grade 4, 12.5%)
Diarrhea (grade 3, 12.5%)
Diarrhea (grade 4, 12.5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
20 mg/m2 3 times / day multiple, oral
MTD
Dose: 20 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 14%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
175 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 175 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 175 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 28.6%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
175 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 175 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 175 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
DLT: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3, 14.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
220 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 220 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 220 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
DLT: Neutropenia, Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3, 25%)
Neutropenia (grade 4, 25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
DLT: Leukopenia, Neutropenia...
Disc. AE: Nausea and vomiting, Fatigue...
Dose limiting toxicities:
Leukopenia (grade 4, 12%)
Neutropenia (grade 4, 25%)
Leukopenia (grade 3, 29%)
Neutropenia (grade 3, 20%)
Thrombocytopenia (grade 4, 4%)
AEs leading to
discontinuation/dose reduction:
Nausea and vomiting (3%)
Fatigue (1%)
Neutropenic sepsis (grade 5, 2%)
Bleeding (grade 5, 1%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
100 mg/m2 1 times / day multiple, intravenous (max)
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020457s013lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020457s013lbl.pdf
Page: p.1
Disc. AE: Myelosuppression...
AEs leading to
discontinuation/dose reduction:
Myelosuppression (severe)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020457s013lbl.pdf
Page: p.1
AEs

AEs

AESignificanceDosePopulation
Diarrhea grade 3, 12.5%
DLT
25 mg/m2 3 times / day multiple, oral
Highest studied dose
Dose: 25 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 25 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
Leukopenia grade 4, 12.5%
DLT
25 mg/m2 3 times / day multiple, oral
Highest studied dose
Dose: 25 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 25 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
Thrombocytopenia grade 4, 12.5%
DLT
25 mg/m2 3 times / day multiple, oral
Highest studied dose
Dose: 25 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 25 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
Diarrhea grade 4, 12.5%
DLT, Disc. AE
25 mg/m2 3 times / day multiple, oral
Highest studied dose
Dose: 25 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 25 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
Neutropenia grade 4, 25%
DLT
25 mg/m2 3 times / day multiple, oral
Highest studied dose
Dose: 25 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 25 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
Neutropenia grade 4, 14%
DLT
20 mg/m2 3 times / day multiple, oral
MTD
Dose: 20 mg/m2, 3 times / day
Route: oral
Route: multiple
Dose: 20 mg/m2, 3 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
unhealthy, 1.1-17
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 1.1-17
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/8021737
Page: p.1455
Neutropenia grade 4, 28.6%
DLT
175 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 175 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 175 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
Neutropenia grade 3, 14.3%
DLT
175 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 175 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 175 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 7
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
Neutropenia grade 3, 25%
DLT
220 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 220 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 220 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
Neutropenia grade 4, 25%
DLT
220 mg/m2 1 times / day multiple, intravenous
MTD
Dose: 220 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 220 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
unhealthy, 39-72
n = 8
Health Status: unhealthy
Condition: Cancer
Age Group: 39-72
Sex: M+F
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/7799021
Page: p.203
Fatigue 1%
Disc. AE
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Nausea and vomiting 3%
Disc. AE
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Neutropenia grade 3, 20%
DLT
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Leukopenia grade 3, 29%
DLT
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Leukopenia grade 4, 12%
DLT
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Neutropenia grade 4, 25%
DLT
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Thrombocytopenia grade 4, 4%
DLT
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Bleeding grade 5, 1%
Disc. AE
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Neutropenic sepsis grade 5, 2%
Disc. AE
60 mg/m2 1 times / day multiple, oral (max)
Recommended
Dose: 60 mg/m2, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg/m2, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
unhealthy, 39-83
n = 97
Health Status: unhealthy
Condition: Ovarian carcinoma
Age Group: 39-83
Sex: F
Population Size: 97
Sources:
https://pubmed.ncbi.nlm.nih.gov/9469322
Page: p.407
Myelosuppression severe
Disc. AE
100 mg/m2 1 times / day multiple, intravenous (max)
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020457s013lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Testicular cancer
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020457s013lbl.pdf
Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

OverviewOther

Other InhibitorOther SubstrateOther Inducer
MRP2
383
OATP1B1
406

P-gp
1537

CYP2E1
667

CYP1A2
1054

CYP3A5
395

CYP2B6
664

CYP2A6
543

UGT1A1
418

UGT1A8
283

UGT1A3
422

UGT1A4
347

UGT1A6
307

UGT1A7
236

UGT1A9
380

UGT1A10
291

UGT2B4
249

UGT2B7
389

UGT2B15
203

UGT2B17
213

Abcc2
3

Abcc3
3

MRP2
205

MRP3
50
CYP3A5
76
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP3A5
130
 slight
MRP2
475
 weak [Ki 756 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
weak (co-administration study)
Comment: Ketoconazole increased the area under the plasma concentration-time curve (AUC) of oral etoposide by a median of 20%
UGT1A1
418
 major
yes (pharmacogenomic study)
Comment: UGT1A1*28 and UGT1A1*6 mutations might be regarded as predictors for etoposide-induced grade 4 neutropenia.
CYP1A2
1054
 minor
CYP2E1
667
 minor
UGT1A3
422
 minor
UGT1A8
283
 minor
CYP2A6
543
 no
CYP2B6
664
 no
UGT1A10
291
 no
UGT1A4
347
 no
UGT1A6
307
 no
UGT1A7
236
 no
UGT1A9
380
 no
UGT2B15
203
 no
UGT2B17
213
 no
UGT2B4
249
 no
UGT2B7
389
 no
Abcc2
3
 yes
Abcc3
3
 yes
ETOPOSIDE GLUCURONIDE
3
CYP3A5
395
 yes
MRP2
205
 yes
MRP3
50
 yes
ETOPOSIDE GLUCURONIDE
3
OATP1B1
406
 yes
P-gp
1537
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4911
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4911
MolPort
MolPort-006-069-121
https://www.molport.com/shop/molecule-link/MolPort-006-069-121
Selleck Chemicals
Etopophos
http://www.selleckchem.com/products/Etopophos.html
ZINC
ZINC000003938684
http://zinc15.docking.org/substances/ZINC000003938684
eMolecules
32278021
https://www.emolecules.com/cgi-bin/more?vid=32278021
eMolecules
537894
https://www.emolecules.com/cgi-bin/more?vid=537894
PubMed

PubMed

TitleDatePubMed
Bone morphogenetic protein-2 promotes osteoblast apoptosis through a Smad-independent, protein kinase C-dependent signaling pathway.
2001 Aug 3
High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results.
2001 May
Irinotecan: future directions in small-cell lung cancer.
2001 May
Langerhans cell histiocytosis.
2001 Nov
Expression of P-glycoprotein and multidrug resistance associated protein in Ehrlich ascites tumor cells after fractionated irradiation.
2001 Nov 15
Alpha-CD25 antibody treatment in a child with hemophagocytic lymphohistiocytosis.
2002 Feb
Coexisting true hermaphroditism and partial hydatidiform mole developing metastatic gestational trophoblastic tumors. A case report.
2002 Nov
Detection of topoisomerase inhibitor-induced DNA strand breaks and apoptosis by the alkaline comet assay.
2002 Sep 26
EBNA1 may prolong G(2)/M phase and sensitize HER2/neu-overexpressing ovarian cancer cells to both topoisomerase II-targeting and paclitaxel drugs.
2003 Aug 1
Inhibition of telomerase activity in malignant glioma cells correlates with their sensitivity to temozolomide.
2003 Sep 1
Phase I dose escalation study of carboplatin to a fixed dose of irinotecan as first-line treatment of small cell lung cancer.
2004 Jun
High-throughput technology: green fluorescent protein to monitor cell death.
2005
Long-term results of autologous stem cell transplantation for Hodgkin's disease (HD) and low-/intermediate-grade B non-Hodgkin's lymphoma (NHL): a report from the Austrian Stem Cell Transplantation Registry (ASCTR).
2005 Jul
Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation.
2005 Jun
Evaluation of the combined effect of p53 codon 72 polymorphism and hotspot mutations in response to anticancer drugs.
2005 Jun 15
HER-2/neu and CD117 (c-kit) overexpression in patients with pesticide exposure and extensive stage small cell lung carcinoma (ESSCLC).
2005 Jun 9
Use of preclinical models to improve treatment of retinoblastoma.
2005 Oct
Adenine nucleotides inhibit proliferation of the human lung adenocarcinoma cell line LXF-289 by activation of nuclear factor kappaB1 and mitogen-activated protein kinase pathways.
2006 Aug
Sequential oral 9-nitrocamptothecin and etoposide: a pharmacodynamic- and pharmacokinetic-based phase I trial.
2006 Aug
Bcl-XL is qualitatively different from and ten times more effective than Bcl-2 when expressed in a breast cancer cell line.
2006 Aug 23
[Pulmonary and pleural manifestations of multiple myeloma].
2006 Dec
Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer.
2006 May 1
Signaling from p53 to NF-kappaB determines the chemotherapy responsiveness of neuroblastoma.
2006 Nov
BRCA1- and BRCA2-deficient cells are sensitive to etoposide-induced DNA double-strand breaks via topoisomerase II.
2007 Aug 1
Dielectrophoretic detection of membrane morphology changes in Jurkat T-cells undergoing etoposide-induced apoptosis.
2007 Feb
Modulation of topoisomerase IIalpha expression by a DNA sequence-specific polyamide.
2007 Jan
Incidence and risk factors of central nervous system recurrence in aggressive lymphoma--a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL).
2007 Jan
The N-terminus and alpha-5, alpha-6 helices of the pro-apoptotic protein Bax, modulate functional interactions with the anti-apoptotic protein Bcl-xL.
2007 May 23
Expression of CYP3A4 as a predictor of response to chemotherapy in peripheral T-cell lymphomas.
2007 Nov 1
A Contribution to solve the problem of the need for consolidative radiotherapy after intensive chemotherapy in advanced stages of Hodgkin's lymphoma--analysis of a quality control program initiated by the radiotherapy reference center of the German Hodgkin Study Group (GHSG).
2007 Nov 15
In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen.
2007 Sep 15
Therapy-associated genetic aberrations in patients treated for non-Hodgkin lymphoma.
2008 Apr
Glassy cell carcinoma of the uterine cervix responsive to neoadjuvant intraarterial chemotherapy.
2008 Dec
Interferonalpha enhances etoposide-induced apoptosis in human osteosarcoma U2OS cells by a p53-dependent pathway.
2008 Feb 13
Treatment experiences of testicular cancer in Hispanic patients with Down's syndrome at the National Cancer Institute of Mexico.
2008 Nov
Haematopoietic stem cell transplantation for autoimmune disorders.
2008 Nov
[Diabetes insipidus followed, after 4 years, with dysarthria and mild right-sided hemiparesis--the first clinical signs of Erdheim-Chester disease. Description and depiction of a case with a review of information on the disease].
2009 Dec
Fasting and cancer treatment in humans: A case series report.
2009 Dec 31
Pegylated liposomal doxorubicin in ovarian cancer.
2009 Jun
Palonosetron in prevention of nausea and vomiting after highly emetogenic chemotherapy before haematopoietic stem cell transplantation-single center experience.
2009 Oct
Etoposide induces MLL rearrangements and other chromosomal abnormalities in human embryonic stem cells.
2009 Sep
Chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone.
2010
Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy.
2010 Aug 23
Mitochondrial fission and cristae disruption increase the response of cell models of Huntington's disease to apoptotic stimuli.
2010 Dec
Cellular responses to etoposide: cell death despite cell cycle arrest and repair of DNA damage.
2010 Feb
The role of an all-oral chemotherapy containing lomustine (CCNU) in advanced,fs progressive Hodgkin lymphoma: a patient-friendly palliative option which can result in long-term disease control.
2010 Feb
Preclinical pharmacology of BA-TPQ, a novel synthetic iminoquinone anticancer agent.
2010 Jul 13
Role of dephosphorylation of FOXO1 on apoptosis induced by wortmannin for non-Hodgkin's lymphoma cells.
2010 Jun
Outpatient reduced-intensity allogeneic stem cell transplantation for patients with refractory or relapsed lymphomas compared with autologous stem cell transplantation using a simplified method.
2010 Oct
Management of non-gestational ovarian choriocarcinoma: laparoscopy can be essential. Report of two cases.
2010 Sep
Patents

Patents

JP2000191546A
3
JP2003175058A
13
JP2003503157A
4
JP2006502184A
41
JP2006523607A
9
JP2008510795A
76
JP2009531296A
19
JP2010530906A
11
JP2011501962A
8
JP2011525178A
25
JP2011528275A
455
JP2012500104A
107
JP4397691B2
21
JP4663232B2
15
JP4744875B2
29
JP4758063B2
4
JPH00597675A
7
JPH02292295A
3
JPH09221495A
3
JPS6461423A
3

Sample Use Guides

In Vivo Use Guide
Curator's Comment: the recommended dose of VePesid (Etoposide) Capsules is two times the IV dose rounded to the nearest 50 mg
50 to 100 mg/m2/day on days 1 through 5 to 100 mg/m2/day on days 1, 3, and 5 (testicular cancer) 35 mg/m2/day for 4 days to 50 mg/m2/day for 5 days (small cell lung cancer)
Route of Administration: Intravenous
In Vitro Use Guide
Apoptosis of thymocytes has been investigated by morphological, biochemical and cytometric techniques, both in non-perturbed conditions and after exposure to the topoisomerase-II inhibitor etoposide in vitro. At low (0.1 to 10 uM) etoposide concentrations apoptotic cells had cytoplasm patterns similar to naturally occurring apoptotic thymocytes, whereas at high (50 to 100 uM) concentrations extensive organelle damage took place.
Substance Class Chemical
Created
by admin
on Sat Dec 16 12:12:52 UTC 2023
Edited
by admin
on Sat Dec 16 12:12:52 UTC 2023
Record UNII
A59HL2Q48U
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ETOPOSIDE TONIRIBATE
INN  
Official Name English
CARBONIC ACID, (2,2-DIMETHYL-1,3-DIOXOLAN-4-YL)METHYL 4-((5R,5AR,8AR,9S)-9-((4,6-O-(1R)-ETHYLIDENE-.BETA.-D-GLUCOPYRANOSYL)OXY)-5,5A,6,8,8A,9-HEXAHYDRO-6-OXOFURO(3',4':6,7)NAPHTHO(2,3-D)-1,3-DIOXOL-5-YL)-2,6-DIMETHOXYPHENYL ESTER
Systematic Name English
PROVP-16I
Common Name English
((4RS)-2,2-DIMETHYL-1,3-DIOXOLAN-4-YL)METHYL4-((5R,5AR,8AR,9S)-9-((4,6-O-((1R)-ETHANE-1,1-DIYL)-.BETA.-D-GLUCOPYRANOSYL)OXY)-6-OXO-5,5A,6,8,8A,9-HEXAHYDRO-2H-FURO(3',4':6,7)NAPHTHO(2,3-D)(1,3)DIOXOL-5-YL)-2,6-DIMETHOXYPHENYL CARBONATE
Systematic Name English
etoposide toniribate [INN]
Common Name English
CAP-7.1
Common Name English
(4-((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)-8-OXO-5A,6,8A,9-TETRAHYDRO-5H-ISOBENZOFURO(5,6-F)(1,3)BENZODIOXOL-9-YL)-2,6-DIMETHOXY-PHENYL) (2,2-DIMETHYL-1,3-DIOXOLAN-4-YL)M
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 671318
Created by admin on Sat Dec 16 12:12:52 UTC 2023 , Edited by admin on Sat Dec 16 12:12:52 UTC 2023
Code System Code Type Description
CAS
433304-61-1
Created by admin on Sat Dec 16 12:12:52 UTC 2023 , Edited by admin on Sat Dec 16 12:12:52 UTC 2023
PRIMARY
NCI_THESAURUS
C114977
Created by admin on Sat Dec 16 12:12:53 UTC 2023 , Edited by admin on Sat Dec 16 12:12:53 UTC 2023
PRIMARY
FDA UNII
A59HL2Q48U
Created by admin on Sat Dec 16 12:12:53 UTC 2023 , Edited by admin on Sat Dec 16 12:12:53 UTC 2023
PRIMARY
PUBCHEM
101163123
Created by admin on Sat Dec 16 12:12:53 UTC 2023 , Edited by admin on Sat Dec 16 12:12:53 UTC 2023
PRIMARY
INN
10430
Created by admin on Sat Dec 16 12:12:53 UTC 2023 , Edited by admin on Sat Dec 16 12:12:53 UTC 2023
PRIMARY
EU-Orphan Drug
EU/3/14/1270
Created by admin on Sat Dec 16 12:12:52 UTC 2023 , Edited by admin on Sat Dec 16 12:12:52 UTC 2023
PRIMARY On 4 June 2014, orphan designation (EU/3/14/1270) was granted by the European Commission to CellAct Pharma GmbH, Germany, for (5R,5aR,8aR,9S)-9-[[4,6-O-[(R)-Ethylidene]-β-D-glucopyranosyl]-oxy]-5-(4-({[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]carbonyl}oxy)-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydroisobenzofuro[5,6-f][1,3]benzodioxol-6(5aH)-one for the treatment of biliary tract cancer.
SMS_ID
100000183902
Created by admin on Sat Dec 16 12:12:53 UTC 2023 , Edited by admin on Sat Dec 16 12:12:53 UTC 2023
PRIMARY
Related Record Type Details
Structure of ETOPOSIDE
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
Structure of ETOPOSIDE
ACTIVE MOIETY
NIH
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