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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H16F2N2O4
Molecular Weight 398.3595
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIFLOMOTECAN

SMILES

CC[C@@]1(O)CC(=O)OCC2=C1C=C3N(CC4=CC5=CC(F)=C(F)C=C5N=C34)C2=O

InChI

InChIKey=LFQCJSBXBZRMTN-OAQYLSRUSA-N
InChI=1S/C21H16F2N2O4/c1-2-21(28)7-18(26)29-9-12-13(21)5-17-19-11(8-25(17)20(12)27)3-10-4-14(22)15(23)6-16(10)24-19/h3-6,28H,2,7-9H2,1H3/t21-/m1/s1

HIDE SMILES / InChI
Molecular Formula C21H16F2N2O4
Molecular Weight 398.3595
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/17322542 | http://adisinsight.springer.com/drugs/800012106

Diflomotecan is an E-ring modified camptothecin analogue, which possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors. Diflomotecan was the first homocamptothecin to enter clinical studies. Phase I data are summarized for both the intravenous and oral schedules. The toxicity is primarily haematological while no severe gastrointestinal toxicity has been observed in contrast to other topoisomerase I inhibitors. Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated. Diflomotecan had been in Phase II clinical trials for the treatment of small cell lung cancer. However, this research has been discontinued.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
31.04 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
37.7 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
3 mg 1 times / 3 weeks multiple, intravenous
dose: 3 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
45.25 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
4 mg 1 times / 3 weeks multiple, intravenous
dose: 4 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
114.5 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
120 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
3 mg 1 times / 3 weeks multiple, intravenous
dose: 3 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
156.83 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
4 mg 1 times / 3 weeks multiple, intravenous
dose: 4 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.32 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4.56 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
3 mg 1 times / 3 weeks multiple, intravenous
dose: 3 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
3.26 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18654747
4 mg 1 times / 3 weeks multiple, intravenous
dose: 4 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
DIFLOMOTECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
DLT: Neutropenia, fatigue...
Other AEs: Thrombocytopenia, anemia...
Dose limiting toxicities:
Neutropenia (grade 4, 3 patients)
fatigue (grade 3, 3 patients)
Other AEs:
Thrombocytopenia (grade 4, 2 patients)
anemia (grade 3, 2 patients)
Vomiting (grade 3, 1 pt)
Diarrhea (grade 2, 2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
5 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
MTD
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 5 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 4
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
DLT: Neutropenia, fatigue...
Other AEs: febrile neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 3 patients)
fatigue (grade 3, 3 patients)
Other AEs:
febrile neutropenia (grade 5, 1 pt)
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
AEs

AEs

AESignificanceDosePopulation
Diarrhea grade 2, 2 patients
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
Vomiting grade 3, 1 pt
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
anemia grade 3, 2 patients
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
fatigue grade 3, 3 patients
DLT
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
Thrombocytopenia grade 4, 2 patients
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
Neutropenia grade 4, 3 patients
DLT
6 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
Highest studied dose
Dose: 6 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 6 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 3
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
fatigue grade 3, 3 patients
DLT
5 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
MTD
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 5 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 4
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
Neutropenia grade 4, 3 patients
DLT
5 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
MTD
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 5 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 4
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
febrile neutropenia grade 5, 1 pt
5 mg/m2 1 times / 3 weeks multiple, intravenous (total daily dose)
MTD
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 5 mg/m2, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
unhealthy
n = 4
Health Status: unhealthy
Condition: malignant solid tumour
Sex: M+F
Food Status: UNKNOWN
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/16261364
Sourcing

Sourcing

Vendor/AggregatorIDURL
MuseChem
R028564
https://www.musechem.com/product/R028564.html
PubMed

PubMed

TitleDatePubMed
A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy.
2009 Apr
Diflomotecan, a promising homocamptothecin for cancer therapy.
2009 Jan
Semimechanistic cell-cycle type-based pharmacokinetic/pharmacodynamic model of chemotherapy-induced neutropenic effects of diflomotecan under different dosing schedules.
2015 Jul
Patents

Patents

US20040259834
1

Sample Use Guides

In Vivo Use Guide
20-min infusion, once every 3 weeks at escalating doses of 2, 4, 5, and 6 mg/m2
Route of Administration: Intravenous
In Vitro Use Guide
BN 80915 inhibits the growth of HT-29 cells with an IC50 around 2 nM after 72 h of continuous drug exposure.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:29:48 UTC 2023
Edited
by admin
on Fri Dec 15 15:29:48 UTC 2023
Record UNII
QKT1LC4J1P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIFLOMOTECAN
INN   WHO-DD  
INN  
Official Name English
(5R)-5-ETHYL-9,10-DIFLUORO-1,4,5,13-TETRAHYDRO-5-HYDROXY-3H,15H-OXEPINO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,15-DIONE
Systematic Name English
Diflomotecan [WHO-DD]
Common Name English
diflomotecan [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2843
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
Code System Code Type Description
MESH
C424962
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
SMS_ID
100000174969
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
INN
7918
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
FDA UNII
QKT1LC4J1P
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
ChEMBL
CHEMBL306280
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
EPA CompTox
DTXSID201026358
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
CAS
220997-97-7
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
WIKIPEDIA
Diflomotecan
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
PUBCHEM
219023
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
NCI_THESAURUS
C90824
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
CHEBI
144046
Created by admin on Fri Dec 15 15:29:48 UTC 2023 , Edited by admin on Fri Dec 15 15:29:48 UTC 2023
PRIMARY
Related Record Type Details
DNA TOPOISOMERASE 1
TARGET -> INHIBITOR
Related Record Type Details
Structure of DIFLOMOTECAN
ACTIVE MOIETY
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