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
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
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 |
DescriptionSources: http://www.ncbi.nlm.nih.gov/pubmed/23232808Curator's Comment: description was created based on several sources, including, http://www.ncbi.nlm.nih.gov/pubmed/19906760
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23232808
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
Sources: http://www.ncbi.nlm.nih.gov/pubmed/15973567
Curator's Comment: In 2003 Novartis licensed the drug from Sigma Tau.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
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
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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%) Sources: Page: p.377Anorexia (grade 4, 9%) Dehydration (9%) |
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%) Sources: Page: p.377Fatigue (grade 3-4, 28.6%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
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
Sample Use Guides
In Vivo Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23232808
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
Sources: http://www.ncbi.nlm.nih.gov/pubmed/11585754
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
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admin
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Edited
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Record UNII |
7KKS9R192F
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C1742
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EU-Orphan Drug |
EU/3/03/174
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NCI_THESAURUS |
C2843
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SUB35137
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C65804
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ACTIVE MOIETY |
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