GIMATECAN

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 Search

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

Description
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
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

Condition	Modality	Highest Phase	Product
Glioblastoma 65 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23232808	Primary	Phase II 1132	Unknown Approved Use Unknown
Epithelial ovarian cancer 2 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19906760	Primary	Phase II 1132	Unknown Approved Use Unknown
Fallopian tube cancer 17 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19906760	Primary	Phase II 1132	Unknown Approved Use Unknown
Peritoneal cancer 11 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19906760	Primary	Phase II 1132	Unknown Approved Use Unknown
Malignant glioma 10 Sources: https://clinicaltrials.gov/ct2/show/NCT00032903	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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: 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

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: 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

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Potent antitumor activity and improved pharmacological profile of ST1481, a novel 7-substituted camptothecin.	2001 Oct 1	11585754
Pattern of antitumor activity of a novel camptothecin, ST1481, in a large panel of human tumor xenografts.	2002 Dec	12473606
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	17150998
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	19118068
DNA damage persistence as determinant of tumor sensitivity to the combination of Topo I inhibitors and telomere-targeting agents.	2011 Apr 15	21355072

Patents

Sample Use Guides

In Vivo Use Guide

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.

Name

Type

Language

GIMATECAN

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