WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201340
CAS#: 171335-80-1 (free base)
Description: Exatecan, also known as DX 8951, is a semisynthetic, water-soluble derivative of camptothecin 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.
MedKoo Cat#: 201340
Name: Exatecan free base
CAS#: 171335-80-1 (free base)
Chemical Formula: C24H22FN3O4
Exact Mass: 435.1594
Molecular Weight: 435.4554
Elemental Analysis: C, 66.20; H, 5.09; F, 4.36; N, 9.65; O, 14.70
Synonym: DX 8951; DX 8951; DX 8951; Exatecan free base.
IUPAC/Chemical Name: (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
InChi Key: ZVYVPGLRVWUPMP-FYSMJZIKSA-N
InChi Code: InChI=1S/C24H22FN3O4/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/h6-7,16,31H,3-5,8-9,26H2,1-2H3/t16-,24-/m0/s1
SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C5C6=C(CC[C@@H]5N)C(C)=C(F)C=C6N=C4C3=C2)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||Topoisomerase I|
|In vitro activity:||Trastuzumab conjugates consisting of exatecan derivatives were prepared and their biological activities and physicochemical properties were evaluated. The ADCs showed strong efficacy and a low aggregation rate. The exatecan derivatives were covalently connected via a peptidyl spacer (Gly-Gly-Phe-Gly), which is assumed to be stable in circulation, and were cleaved by lysosomal enzymes following ADC internalization into tumor tissue. These anti-HER2 ADCs exhibited a high potency, specifically against HER2-positive cancer cell lines in vitro. The ADCs, bearing exatecan derivatives which have more than two methylene chains, exhibited superior cytotoxicity. It was speculated that steric hindrance of the cleavable amide moiety could be involved in the drug release. The adequate alkyl lengths of exatecan derivatives (13, 14, 15) were from two to four in terms of aggregation rate. The ADC having a hydrophilic moiety showed good efficacy in a HER2-positive and Trastuzumab-resistant breast carcinoma cell model in mice. Reference: 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):1542-1545. doi: 10.1016/j.bmcl.2016.02.020. Epub 2016 Feb 8. PMID: 26898815.|
|In vivo activity:||DS-8201a resulted in favorable outcomes in HER2-positive heavily pretreated breast cancer patients and also had a promising efficacy in patients with HER2-negative/low-expressing disease, whose options are limited. Interestingly, a recently published phase 2 trial (NCT03248492) reported 60% overall response and 97% disease control in patients with HER2-positive disease previously treated with multiple regimens, including trastuzumab emtansine. On the basis of recent clinical trials, the US Food and Drug Administration granted accelerated approval to DS-8201a in advanced or unresectable HER2-positive breast cancer pretreated with at least two HER2-targeting treatment lines. All preclinical and clinical data of DS-8201a regarding breast cancer was reviewed. Reference: Andrikopoulou A, Zografos E, Liontos M, Koutsoukos K, Dimopoulos MA, Zagouri F. Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer. Clin Breast Cancer. 2021 Jun;21(3):e212-e219. doi: 10.1016/j.clbc.2020.08.006. Epub 2020 Aug 18. PMID: 32917537.|
The following data is based on the product molecular weight 435.4554 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||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):1542-1545. doi: 10.1016/j.bmcl.2016.02.020. Epub 2016 Feb 8. PMID: 26898815.|
|In vitro protocol:||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):1542-1545. doi: 10.1016/j.bmcl.2016.02.020. Epub 2016 Feb 8. PMID: 26898815.|
|In vivo protocol:||Andrikopoulou A, Zografos E, Liontos M, Koutsoukos K, Dimopoulos MA, Zagouri F. Trastuzumab Deruxtecan (DS-8201a): The Latest Research and Advances in Breast Cancer. Clin Breast Cancer. 2021 Jun;21(3):e212-e219. doi: 10.1016/j.clbc.2020.08.006. Epub 2020 Aug 18. PMID: 32917537.|
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.
6: Braybrooke JP, Ranson M, Manegold C, Mattson K, Thatcher N, Cheverton P, Sekiguchi M, Suzuki M, Oyama R, Talbot DC. Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer. Lung Cancer. 2003 Aug;41(2):215-9. PubMed PMID: 12871785.
7: Esteva FJ, Rivera E, Cristofanilli M, Valero V, Royce M, Duggal A, Colucci P, DeJager R, Hortobagyi GN. A Phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with metastatic breast carcinoma. Cancer. 2003 Sep 1;98(5):900-7. PubMed PMID: 12942555.
8: Clamp A, Adams M, Atkinson R, Boven E, Calvert AH, Cervantes A, Ganesan T, Lotz J, Vasey P, Cheverton P, Jayson GC. 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. Gynecol Oncol. 2004 Oct;95(1):114-9. PubMed PMID: 15385119.
9: Wente MN, Kleeff J, Büchler MW, Wanders J, Cheverton P, Langman S, Friess H. DE-310, a macromolecular prodrug of the topoisomerase-I-inhibitor exatecan (DX-8951), in patients with operable solid tumors. Invest New Drugs. 2005 Aug;23(4):339-47. PubMed PMID: 16012793.
10: Owen OG. Exatecan and gemcitabine: no better than gemcitabine only. Lancet Oncol. 2006 Nov;7(11):891. PubMed PMID: 17106952.
11: Ajani JA, Takimoto C, Becerra CR, Silva A, Baez L, Cohn A, Major P, Kamida M, Feit K, De Jager R. A phase II clinical and pharmacokinetic study of intravenous exatecan mesylate (DX-8951f) in patients with untreated metastatic gastric cancer. Invest New Drugs. 2005 Oct;23(5):479-84. PubMed PMID: 16133799.
12: Braybrooke JP, Boven E, Bates NP, Ruijter R, Dobbs N, Cheverton PD, Pinedo HM, Talbot DC. Phase I and pharmacokinetic study of the topoisomerase I inhibitor, exatecan mesylate (DX-8951f), using a weekly 30-minute intravenous infusion, in patients with advanced solid malignancies. Ann Oncol. 2003 Jun;14(6):913-21. PubMed PMID: 12796030.
13: Minami H, Fujii H, Igarashi T, Itoh K, Tamanoi K, Oguma T, Sasaki Y. Phase I and pharmacological study of a new camptothecin derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every three weeks. Clin Cancer Res. 2001 Oct;7(10):3056-64. PubMed PMID: 11595695.
14: Royce ME, Rowinsky EK, Hoff PM, Coyle J, DeJager R, Pazdur R, Saltz LB. A phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for five days every three weeks to patients with metastatic adenocarcinoma of the colon or rectum. Invest New Drugs. 2004 Jan;22(1):53-61. PubMed PMID: 14707494.
15: Verschraegen CF, Kudelka AP, Hu W, Vincent M, Kavanagh JJ, Loyer E, Bastien L, Duggal A, De Jager R. 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. Cancer Chemother Pharmacol. 2004 Jan;53(1):1-7. PubMed PMID: 14586557.
16: Sharma S, Kemeny N, Schwartz GK, Kelsen D, O'Reilly E, Ilson D, Coyle J, De Jager RL, Ducharme MP, Kleban S, Hollywood E, Saltz LB. Phase I study of topoisomerase I inhibitor exatecan mesylate (DX-8951f) given as weekly 24-hour infusions three of every four weeks. Clin Cancer Res. 2001 Dec;7(12):3963-70. PubMed PMID: 11751488.
17: Sun FX, Tohgo A, Bouvet M, Yagi S, Nassirpour R, Moossa AR, Hoffman RM. Efficacy of camptothecin analog DX-8951f (Exatecan Mesylate) on human pancreatic cancer in an orthotopic metastatic model. Cancer Res. 2003 Jan 1;63(1):80-5. PubMed PMID: 12517781.
18: Royce ME, Hoff PM, Dumas P, Lassere Y, Lee JJ, Coyle J, Ducharme MP, De Jager R, Pazdur R. Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): a novel camptothecin analog. J Clin Oncol. 2001 Mar 1;19(5):1493-500. PubMed PMID: 11230496.
19: Giles FJ, Cortes JE, Thomas DA, Garcia-Manero G, Faderl S, Jeha S, De Jager RL, Kantarjian HM. Phase I and pharmacokinetic study of DX-8951f (exatecan mesylate), a hexacyclic camptothecin, on a daily-times-five schedule in patients with advanced leukemia. Clin Cancer Res. 2002 Jul;8(7):2134-41. PubMed PMID: 12114413.
20: Oguma T, Yamada M, Konno T, Inukai K, Nakaoka M. High-Performance liquid chromatographic analysis of lactone and hydroxy acid of new antitumor drug, DX-8951 (exatecan), in mouse plasma. Biol Pharm Bull. 2001 Feb;24(2):176-80. PubMed PMID: 11217088.