Exatecan Mesylate

Exatecan Mesylate, also known as DX 8951, is semisynthetic, water-soluble camptothecin derivative with antineoplastic activity. Exatecan mesylate inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA and inhibiting religation of DNA breaks, thereby inhibiting DNA replication and triggering apoptotic cell death. This agent does not require enzymatic activation and exhibits greater potency than camptothecin and other camptothecin analogues.

Product information

CAS Number: 169869-90-3

Molecular Weight: 531.55

Formula: C25H26FN3O7S

Synonym:

DX 8951

DX-8951

DX8951

Exatecan mesylate

Related CAS Number:

169869-90-3 (mesylate)

171335-80-1 (free base)

Chemical Name: (10S, 23S)-23-amino-10-ethyl-18-fluoro-10-hydroxy-19-methyl-8-oxa-4, 15-diazahexacyclo[14.7.1.0, .0, .0, .0, ]tetracosa-1, 6(11), 12, 14, 16, 18, 20(24)-heptaene-5, 9-dione

Smiles: CC1C2CC[C@H](N)C3=C4CN5C(=CC6=C(COC(=O)[C@]6(O)CC)C5=O)C4=NC(=CC=1F)C3=2.CS(O)(=O)=O

InChiKey: BICYDYDJHSBMFS-GRGFAMGGSA-N

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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

Exatecan Mesylate is a potent topoisomerase I inhibitor, with an IC50 of 0.975 μg/mL. Exatecan Mesylate (DX-8951f) significantly inhibits the proliferation of several cancer cell lines, with mean GI50s of 2.02 ng/mL, 2.92 ng/mL, 1.53 ng/mL, and 0.877 ng/mL for breast cancer cells, colon cancer cells, stomach cancer cells and lung cancer cells, respectively. Exatecan Mesylate (DX-8951f) displays cytotoxic activities against PC-6, PC-6/SN2-5 cells, with mean GI50s of 0.186 and 0.395 ng/mL, respctively. Exatecan Mesylate (34 nM) stabilizes DNA-TopoI complexes in PC-6 and PC-6/SN2-5 cells.

In Vivo:

Exatecan Mesylate (DX-8951f, 3.325-50 mg/kg, i.v.) exhibits antitumor activities in the mice model bearing tumor cells, without toxic death. Exatecan Mesylate (15, 25 mg/kg, i.v.) hightly inhibits MIA-PaCa, BxPC-3 primary tumor growth in the MIA-PaCa-2 early-stage model and early-stage model of BxPC-3. Exatecan Mesylate (15, 25 mg/kg, i.v.) also significantly suppresses BxPC-3 lymphatic metastasis and completely eliminates lung metastasis in the BxPC-3 late-stage cancer model.

References:

1. Nakada T, Masuda T, Naito H, Yoshida M, Ashida S, Morita K, Miyazaki H, Kasuya Y, Ogitani Y, Yamaguchi J, Abe Y, Honda T. Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorg Med Chem Lett. 2016 Mar 15;26(6):1542-5. doi: 10.1016/j.bmcl.2016.02.020. PubMed PMID: 26898815.
2. Abou-Alfa GK, Letourneau R, Harker G, Modiano M, Hurwitz H, Tchekmedyian NS, Feit K, Ackerman J, De Jager RL, Eckhardt SG, O'Reilly EM. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol. 2006 Sep 20;24(27):4441-7. PubMed PMID: 16983112.
3. Reichardt P, Nielsen OS, Bauer S, Hartmann JT, Schöffski P, Christensen TB, Pink D, Daugaard S, Marreaud S, Van Glabbeke M, Blay JY; EORTC Soft Tissue and Bone Sarcoma Group Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2007 Apr;43(6):1017-22. PubMed PMID: 17336054.
4. Garrison MA, Hammond LA, Geyer CE Jr, Schwartz G, Tolcher AW, Smetzer L, Figueroa JA, Ducharme M, Coyle J, Takimoto CH, De Jager RL, Rowinsky EK. A Phase I and pharmocokinetic study of exatecan mesylate administered as a protracted 21-day infusion in patients with advanced solid malignancies. Clin Cancer Res. 2003 Jul;9(7):2527-37. PubMed PMID: 12855627.
5. Abou-Alfa GK, Rowinsky EK, Patt YZ, Schwartz GK, Kelsen DP, Sharma S, Siegel E, Becerra CR, Eckhardt SG, Feit K, De Jager R, O'Reilly EM. A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers. Am J Clin Oncol. 2005 Aug;28(4):334-9. PubMed PMID: 16062073.

Products are for research use only. Not for human use.