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

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

Approval Year

Targets

Targets

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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
86.1 ng/mL
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
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
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
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
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
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
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
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
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
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
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
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: 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: Page: p.377
DLT: Nausea, Anorexia...
Dose limiting toxicities:
Nausea (grade 3, 9%)
Anorexia (grade 4, 9%)
Dehydration (9%)
Sources: 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: 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: Page: p.377
DLT: Hyperbilirubinemia, Fatigue...
Dose limiting toxicities:
Hyperbilirubinemia (grade 2, 14.3%)
Fatigue (grade 3-4, 28.6%)
Sources: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Page: p.377
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
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
Patents

Patents

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
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