Name: Exatecan Mesylate
Brand: BOC Sciences
Price: 298 USD
Availability: MadeToOrder

Size

Price

Stock

Quantity

500 mg

$298

In stock

Synonyms

DX 8951 mesylate; (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 mesylate; 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-trans)-, mesylate (1:1); NSC-829066 mesylate

IUPAC Name

(10S,23S)-23-amino-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4,15-diazahexacyclo[14.7.1.02,14.04,13.06,11.020,24]tetracosa-1,6(11),12,14,16,18,20(24)-heptaene-5,9-dione;methanesulfonic acid

Canonical SMILES

CCC1(C2=C(COC1=O)C(=O)N3CC4=C5C(CCC6=C5C(=CC(=C6C)F)N=C4C3=C2)N)O.CS(=O)(=O)O

InChI

InChI=1S/C24H22FN3O4.CH4O3S/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)/t16-,24-;/m0./s1

InChIKey

BICYDYDJHSBMFS-GRGFAMGGSA-N

Solubility

Soluble in DMSO (Slightly), Methanol (Slightly, Heated, Sonicated), Water (Slightly, Heated)

Melting Point

>137°C (dec.)

Appearance

Pale Yellow to Yellow Solid

Storage

-20 °C

Current Developer

Daiichi Sankyo, Inc.

In Vitro

Exatecan mesylate is a novel topoisomerase I inhibitor with potent activity against ovarian cancer in vitro. A multicentre phase IIA study was conducted in patients with platinum- and taxane-resistant epithelial ovarian cancer. There were no responses in the weekly arm and a radiological response rate of 5.3% (95% CI 0.3-21.8%) in the daily arm. Principal toxicities were myelosuppression and emesis. Grade 3/4 neutropenia occurred in 29% of patients in Arm A and 6% patients in Arm B. Seventy-one percent of patients in Arm A required red cell transfusions while on treatment. Exatecan is well tolerated in this poor prognosis group of patients but only has modest single agent activity when administered in a daily regimen.

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT00003951	Pancreatic Cancer	Phase 2	2012-05-16	Daiichi Sankyo, Inc.	Completed
NCT00005938	Extrahepatic Bile Duct Cancer	Phase 2	2012-05-16	Daiichi Sankyo, Inc.	Completed
NCT00017212	Esophageal Cancer	Phase 2	2012-05-16	Daiichi Sankyo, Inc.	Completed
NCT00023972	Pancreatic Cancer	Phase 3	2012-05-16	Daiichi Sankyo, Inc.	Completed
NCT00004212	Brain and Central Nervous System Tumors	Phase 1	2012-05-16	Daiichi Sankyo, Inc.	Completed

1. 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

Claire F. Verschraegen, Andrzej P. Kudelka, Wei Hu. Cancer Chemother Pharmacol (2004) 53: 1–7

Exatecan mesylate (DX-8951f) is a synthetic derivative of camptothecin, a natural alkaloid extracted from the bark and leaves of the tree, Camptotheca acuminata. The activity of the drug is linked to its lactone form, which is in equilibrium with a carboxylate (open E ring) form. The equilibrium favors the carboxylate form at physiologic pH. The chemical structure of exatecan mesylate (DX-8951f) has been modiﬁed to render the molecule water soluble by adding a ring structure between rings A (in position 9) and B (in position 7), and a ﬂuor in position 11. DX-8951f has shown both high in vitro potency against a series of 32 malignant cell lines and signiﬁcant topoisomerase I inhibition. The antiproliferative activity of exatecan mesylate (DX-8951f) in this system was 28 times greater than that of topotecan, and the antiproliferative activity of DX-8951f was about seven times greater than that of SN-38 (an active metabolite of irinotecan). Because of the demonstration of greater activity of DX-8951f than other camptothecin derivatives at equimolar concentrations in these pre- clinical studies, this phase II study was initiated.

2. DE-310, a macromolecular prodrug of the topoisomerase-I-inhibitor exatecan (DX-8951), in patients with operable solid tumors

Moritz N. Wente1 ,Jorg Kleeff, Markus W. Buchler. Investigational New Drugs 23: 339–347, 2005.

One of the recently introduced members of camptothecin analogs, exatecan mesylate (DX-8951f), is a synthetic water-soluble hexacyclic camptothecin analogue with broad anti-tumor activity. In pre-clinical studies, DX-8951 revealed highly potent inhibition of tumor cell growth in vitro and in vivo,evenin cells resistant to other members of the camptothecin family. In com- parison to other camptothecins, DX-8951 showed up to 20-fold higher topoisomerase-I inhibition and up to 30-fold more potent cell growth inhibition in vitro in various cancer cell lines.With its anti-tumor activity against irinotecan- and topotecan-resistant tumors, in phase II clinical DX-8951 demonstrated anti-tumor activity in several cancer types; phase III studies in pancreatic cancerare ongoing.

3. A phase II clinical and pharmacokinetic study of intravenous exatecan mesylate (DX-8951f) in patients with untreated metastatic gastric cancer

Jaffer A. Ajani, Chris Takimoto, Carlos R. Becerra. Investigational New Drugs 23: 479–484, 2005

Exatecan mesylate (DX-8951f; Daiichi Pharmaceutical Co., Ltd., Japan) is a synthetic camptothecin analogue (Figure 1) that is amore potent inhibitor of topoisomerase I than camptothecin, topotecan, and the active metabolite of irinotecan, SN-38. In preclinical studies, DX-8951f demonstrated broad antitumor activity compared with available camptothecin analogues. Cyclical dosing at lower doses demonstrated higher antitumor activity compared to single dose administration. Furthermore, the antitumor activity documented in phase I trials made DX-8951f an attractive compound for clinical development. We have completed a phase II trial designed to evaluate the activity and toxicity of exatecan mesylate (DX-8951f) in patients with previously untreated gastric carcinoma given as a thirty minute infusion daily for 5 days every 3 weeks. This schedule was selected from six phase I regimens because of the level of antitumor activity observed and its favorable toxicity proﬁle.

HPLC

HNMR