EXATECAN MESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H22FN3O4.CH4O3S.2H2O
Molecular Weight	567.584
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.CS(O)(=O)=O.CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C3N=C5C=C(F)C(C)=C6CC[C@H](N)C4=C56)C2=O

InChI

InChIKey=FXQZOHBMBQTBMJ-MWPGLPCQSA-N

InChI=1S/C24H22FN3O4.CH4O3S.2H2O/c1-3-24(31)14-6-18-21-12(8-28(18)22(29)13(14)9-32-23(24)30)19-16(26)5-4-11-10(2)15(25)7-17(27-21)20(11)19;1-5(2,3)4;;/h6-7,16,31H,3-5,8-9,26H2,1-2H3;1H3,(H,2,3,4);2*1H2/t16-,24-;;;/m0.../s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11193901 | https://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=778296&p_IsPs=N | https://www.ncbi.nlm.nih.gov/pubmed/15991999

Exatecan (DX-8951f), a new hexacyclic camptothecin analogue, is a second-generation topoisomerase inhibitor that prevents rapidly dividing cells from replicating by interrupting DNA transcription, ultimately leading to cell death. Preclinical studies showed exatecan to have broad-spectrum antitumor efficacy. Exatecan is in phase III clinical trials for the treatment of pancreas cancer. However, there is no recent report of this research. The compound was co-developed by Daiichi Pharmaceutical (now Daiichi Sankyo) and Yakult Honsha.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA topoisomerase I 59 Target ID: CHEMBL1781 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27599744 \| https://www.ncbi.nlm.nih.gov/pubmed/11193901 \| https://www.ncbi.nlm.nih.gov/pubmed/15991999 \| https://www.ncbi.nlm.nih.gov/pubmed/9330608	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 97 Sources: https://clinicaltrials.gov/ct2/show/NCT00023972	Primary	Phase III 656	Unknown Approved Use Unknown
Gastric cancer 53 Sources: https://clinicaltrials.gov/ct2/show/NCT00017212	Primary	Phase II 1132	Unknown Approved Use Unknown
Sarcoma 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00055939	Primary	Phase II 1132	Unknown Approved Use Unknown
Liver cancer 53 Sources: https://clinicaltrials.gov/ct2/show/NCT00004108	Primary	Phase II 1132	Unknown Approved Use Unknown
Cervical cancer 40 Sources: https://clinicaltrials.gov/ct2/show/NCT00004866	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
DX-8951f: summary of phase I clinical trials.	2000	11193901
The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer.	2002 Oct 15	12234607
The activity profile of the hexacyclic camptothecin derivative DX-8951f in experimental human colon cancer and ovarian cancer.	2002 Oct 15	12234607
A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with advanced ovarian, tubal or peritoneal cancer resistant to platinum, taxane and topotecan.	2004 Jan	14586557
A phase IIA study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f), administered at two different dose schedules in patients with platinum- and taxane-resistant/refractory ovarian cancer.	2004 Oct	15385119
A predictive model of human myelotoxicity using five camptothecin derivatives and the in vitro colony-forming unit granulocyte/macrophage assay.	2004 Oct 1	15475463

Patents

Sample Use Guides

In Vivo Use Guide

Fifty-seven patients with bidimensionally measurable ovarian cancer, previously exposed to platinum and taxanes, whose disease had relapsed within 6 months of platinum-containing chemotherapy were randomised to one of two intravenous schedules of exatecan mesylate; 0.3 mg/m(2) daily for 5 days every 3 weeks (Arm A) or 2.1 mg/m(2) weekly for 3 weeks out of 4 (Arm B).

Route of Administration: Intravenous

In Vitro Use Guide

Exatecan had superior antitumor efficacy compared to topotecan and irinotecan against all human malignancies tested, with mean IC50 values of 30.8, 48.2, 43.6 and 70.6 ng/ml, respectively, against esophageal, gastric, colorectal and breast cancer lines.

Name

Type

Language

EXATECAN MESYLATE

Official Name

English

EXATECAN METHANESULFONATE DIHYDRATE

Common Name

English

DX-8951F

Code

English

EXATECAN MESILATE HYDRATE [JAN]

Common Name

English

EXATECAN MESILATE DIHYDRATE

Common Name

English

EXATECAN MESILATE HYDRATE

Common Name

English

(1S-TRANS)-1-AMINO-9-ETHYL-5-FLUORO-1,2,3,9,12,15-HEXAHYDRO-9-HYDROXY-4-METHYL-10H, 13H-BENZO(DE)PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-10,13-DIONE MONOMETHANESULFONATE (SALT), DIHYDRATE

Common Name

English

(1S,9S)-1-AMINO-9-ETHYL-5-FLUORO-1,2,3,9,12,15-HEXAHYDRO-9-HYDROXY-4-METHYL-10H, 13H-BENZO(DE)PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-10,13-DIONE MONOMETHANESULFONATE (SALT), DIHYDRATE

Common Name

English

EXATECAN MESYLATE [USAN]

Common Name

English

(1S-TRANS)-1-AMINO-9-ETHYL-5-FLUORO-1,2,3,9,12,15-HEXAHYDRO-9-HYDROXY-4-METHYL-10H, 13H-BENZO(DE)PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-10,13-DIONE MONOMETHANESULPHONATE (SALT), DIHYDRATE

Common Name

English

Exatecan mesilate dihydrate [WHO-DD]

Common Name

English

EXATECAN METHANESULFONATE DIHYDRATE [MI]

Common Name

English

(1S,9S)-1-AMINO-9-ETHYL-5-FLUORO-1,2,3,9,12,15-HEXAHYDRO-9-HYDROXY-4-METHYL-10H, 13H-BENZO(DE)PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-10,13-DIONE MONOMETHANESULPHONATE (SALT), DIHYDRATE

Common Name

English

10H,13H-BENZO(DE)PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-10,13-DIONE, 1-AMINO-9-ETHYL-5-FLUORO-1,2,3,9,12,15-HEXAHYDRO-9-HYDROXY-4-METHYL-, (1S,9S)-, METHANESULFONATE HYDRATE(1:1:2)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2843