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

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H25N3O5
Molecular Weight 447.4831
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of GIMATECAN

SMILES

CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C(\C=N\OC(C)(C)C)C5=CC=CC=C5N=C34)C2=O

InChI

InChIKey=UIVFUQKYVFCEKJ-OPTOVBNMSA-N
InChI=1S/C25H25N3O5/c1-5-25(31)18-10-20-21-16(12-28(20)22(29)17(18)13-32-23(25)30)15(11-26-33-24(2,3)4)14-8-6-7-9-19(14)27-21/h6-11,31H,5,12-13H2,1-4H3/b26-11+/t25-/m0/s1

HIDE SMILES / InChI
Molecular Formula C25H25N3O5
Molecular Weight 447.4831
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including, http://www.ncbi.nlm.nih.gov/pubmed/19906760

Gimatecan is a topoisomerase I inhibitor that is presently tested in phase II of clinical trials for the treatment of different cancers: glioma, glioblastoma, epithelial ovarian cancer, fallopian tube or peritoneal cancer. The drug recieved orphan designation for the treatment of glioma.

Originator

Sigma-Tau
19
Curator's Comment: In 2003 Novartis licensed the drug from Sigma Tau.

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
DNA topoisomerase 1
16
Target ID: P11387|||Q9UJN0
Gene ID: 7150.0
Gene Symbol: TOP1
Target Organism: Homo sapiens (Human)
Sources: www.ncbi.nlm.nih.gov/pubmed/16990856
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
86.1 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
3.2 mg/m² 1 times / week multiple, oral
dose: 3.2 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
66.3 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
3.2 mg/m² single, oral
dose: 3.2 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
66.9 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
2.4 mg/m² 1 times / week single, oral
dose: 2.4 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5.4 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
2.4 mg/m² 1 times / week multiple, oral
dose: 2.4 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
10825 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
3.2 mg/m² 1 times / week multiple, oral
dose: 3.2 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7364 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
3.2 mg/m² single, oral
dose: 3.2 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7757 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
2.4 mg/m² 1 times / week single, oral
dose: 2.4 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
8568 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
2.4 mg/m² 1 times / week multiple, oral
dose: 2.4 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
88.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
3.2 mg/m² 1 times / week multiple, oral
dose: 3.2 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
67.3 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
3.2 mg/m² single, oral
dose: 3.2 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
80.6 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
2.4 mg/m² 1 times / week single, oral
dose: 2.4 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
79.8 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/19118068
2.4 mg/m² 1 times / week multiple, oral
dose: 2.4 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GIMATECAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2.4 mg/m2 1 times / week multiple, oral
MTD
Dose: 2.4 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 11
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
DLT: Nausea, Anorexia...
Dose limiting toxicities:
Nausea (grade 3, 9%)
Anorexia (grade 4, 9%)
Dehydration (9%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
3.2 mg/m2 1 times / week multiple, oral
Studied dose
Dose: 3.2 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 3.2 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
DLT: Hyperbilirubinemia, Fatigue...
Dose limiting toxicities:
Hyperbilirubinemia (grade 2, 14.3%)
Fatigue (grade 3-4, 28.6%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
AEs

AEs

AESignificanceDosePopulation
Dehydration 9%
DLT
2.4 mg/m2 1 times / week multiple, oral
MTD
Dose: 2.4 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 11
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
Nausea grade 3, 9%
DLT
2.4 mg/m2 1 times / week multiple, oral
MTD
Dose: 2.4 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 11
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
Anorexia grade 4, 9%
DLT
2.4 mg/m2 1 times / week multiple, oral
MTD
Dose: 2.4 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 2.4 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 11
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 11
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
Hyperbilirubinemia grade 2, 14.3%
DLT
3.2 mg/m2 1 times / week multiple, oral
Studied dose
Dose: 3.2 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 3.2 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
Fatigue grade 3-4, 28.6%
DLT
3.2 mg/m2 1 times / week multiple, oral
Studied dose
Dose: 3.2 mg/m2, 1 times / week
Route: oral
Route: multiple
Dose: 3.2 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/19118068
Page: p.377
Sourcing

Sourcing

Vendor/AggregatorIDURL
Achemtek
0102-022157
http://www.achemtek.com/292618-32-7
Acorn PharmaTech
ACN-035811
http://www.acornpharmatech.com/
Adooq BioScience
A12856
https://www.adooq.com/gimatecan.html
Chem Scene
CS-0006524
http://www.chemscene.com/292618-32-7.html
ChemMol
44001444
http://www.chemmol.com/chemmol/44001444.html
ChemMol
49400391
http://www.chemmol.com/chemmol/49400391.html
Lab Network
LN01345707
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01345707
MedChem Express
HY-B0063
https://www.medchemexpress.com/gimatecan.html
MolPort
MolPort-005-933-314
https://www.molport.com/shop/molecule-link/MolPort-005-933-314
MuseChem
I006961
https://www.musechem.com/product/I006961.html
OChem
26269
http://www.ocheminc.com/index.php?act=psearch&pid=618G327
eNovation Chemicals
D672850
https://www.enovationchem.com/ProductDetails.asp?ProductID=D672850
iChemical
EBD7896
http://www.ichemical.com/chemicals/cas-292618-32-7
PubMed

PubMed

TitleDatePubMed
Potent antitumor activity and improved pharmacological profile of ST1481, a novel 7-substituted camptothecin.
2001 Oct 1
Pattern of antitumor activity of a novel camptothecin, ST1481, in a large panel of human tumor xenografts.
2002 Dec
Antiangiogenic effects of the novel camptothecin ST1481 (gimatecan) in human tumor xenografts.
2003 Oct
In vitro transport of gimatecan (7-t-butoxyiminomethylcamptothecin) by breast cancer resistance protein, P-glycoprotein, and multidrug resistance protein 2.
2007 Dec
Concerted escalation of dose and dosing duration in a phase I study of the oral camptothecin gimatecan (ST1481) in patients with advanced solid tumors.
2007 Mar
Phase I and pharmacokinetic study of gimatecan given orally once a week for 3 of 4 weeks in patients with advanced solid tumors.
2009 Jan 1
Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes.
2010 Apr
DNA damage persistence as determinant of tumor sensitivity to the combination of Topo I inhibitors and telomere-targeting agents.
2011 Apr 15
Patents

Patents

US7700613 B2
1

Sample Use Guides

In Vivo Use Guide
Curator's Comment: http://www.ncbi.nlm.nih.gov/pubmed/19906760
Glioblastoma: 1.22 mg/m(2) is given orally once daily for 5 consecutive days during each 28-day cycle; epithelial ovarian, fallopian tube or peritoneal cancer: 0.8 mg/m(2)/day is administered orally once daily for 5 consecutive days during each 28-day cycle.
Route of Administration: Oral
In Vitro Use Guide
Cellular sensitivity of H460, A2780, IGROV-1 cell lines to gimatecan (10 uM) was investigated after 1 hour of exposure. IC50 values were 0.01 uM, 0.015 ug/ml, 0.017 ug/ml, respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:15:16 GMT 2023
Edited
by admin
on Sat Dec 16 16:15:16 GMT 2023
Record UNII
7KKS9R192F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GIMATECAN
INN   MART.   WHO-DD  
INN  
Official Name English
Gimatecan [WHO-DD]
Common Name English
gimatecan [INN]
Common Name English
(4S)-11-((E)-((1,1-DIMETHYLETHOXY)IMINO)METHYL)-4-ETHYL-4-HYDROXY-1,12-DIHYDRO-14H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H)-DIONE
Systematic Name English
GIMATECAN [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
EU-Orphan Drug EU/3/03/174
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
NCI_THESAURUS C2843
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
Code System Code Type Description
PUBCHEM
9577124
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
CAS
292618-32-7
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
EVMPD
SUB35137
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
NCI_THESAURUS
C65804
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
FDA UNII
7KKS9R192F
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
ChEMBL
CHEMBL113051
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
INN
8116
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
EPA CompTox
DTXSID0057702
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
DRUG BANK
DB06721
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
SMS_ID
100000128292
Created by admin on Sat Dec 16 16:15:17 GMT 2023 , Edited by admin on Sat Dec 16 16:15:17 GMT 2023
PRIMARY
Related Record Type Details
Structure of CAMPTOTHECIN
PARENT -> DERIVATIVE
DNA TOPOISOMERASE 1
TARGET -> INHIBITOR
Related Record Type Details
Structure of GIMATECAN
ACTIVE MOIETY
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