MedKoo product information:

Edotecarin

Description of Edotecarin: Edotecarin is a synthetic indolocarbazole with antineoplastic activity. Edotecarin inhibits the enzyme topoisomerase I through stabilization of the DNA-enzyme complex and enhanced single-strand DNA cleavage, resulting in inhibition of DNA replication and decreased tumor cell proliferation. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus) .

Current developer:   Banyu (Originator), Merck & Co. (Originator), Pfizer (Licensee).

 1: Saif MW, Sellers S, Diasio RB, Douillard JY. A phase I dose-escalation study of edotecarin (J-107088) combined with infusional 5-fluorouracil and leucovorin in patients with advanced/metastatic solid tumors. Anticancer Drugs. 2010 Aug;21(7):716-23. PubMed PMID: 20581657.

2: Sunami S, Nishimura T, Nishimura I, Ito S, Arakawa H, Ohkubo M. Synthesis and biological activities of topoisomerase I inhibitors, 6-arylmethylamino analogues of edotecarin. J Med Chem. 2009 May 28;52(10):3225-37. PubMed PMID: 19397324.

3: Norden AD, Drappatz J, Muzikansky A, David K, Gerard M, McNamara MB, Phan P, Ross A, Kesari S, Wen PY. An exploratory survival analysis of anti-angiogenic therapy for recurrent malignant glioma. J Neurooncol. 2009 Apr;92(2):149-55. Epub 2008 Nov 29. PubMed PMID: 19043778.

4: Animati F, Berettoni M, Bigioni M, Binaschi M, Felicetti P, Gontrani L, Incani O, Madami A, Monteagudo E, Olivieri L, Resta S, Rossi C, Cipollone A. Synthesis, biological evaluation, and molecular modeling studies of rebeccamycin analogues modified in the carbohydrate moiety. ChemMedChem. 2008 Feb;3(2):266-79. PubMed PMID: 18157856.

5: Teicher BA. Next generation topoisomerase I inhibitors: Rationale and biomarker strategies. Biochem Pharmacol. 2008 Mar 15;75(6):1262-71. Epub 2007 Oct 22. Review. PubMed PMID: 18061144.

6: Bayes M. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):153-73. PubMed PMID: 17440629.

7: Carvajal RD, Ilson DH, Noy A. Possible role of edotecarin, a novel topoisomerase I inhibitor, in therapy-related myelodysplastic syndrome. Leuk Lymphoma. 2007 Jan;48(1):192-4. PubMed PMID: 17325867.

8: Ciomei M, Croci V, Stellari F, Amboldi N, Giavarini R, Pesenti E. Antitumor activity of edotecarin in breast carcinoma models. Cancer Chemother Pharmacol. 2007 Jul;60(2):229-35. Epub 2006 Nov 7. PubMed PMID: 17089166.

9: Hurwitz HI, Cohen RB, McGovren JP, Hirawat S, Petros WP, Natsumeda Y, Yoshinari T. A phase I study of the safety and pharmacokinetics of edotecarin (J-107088), a novel topoisomerase I inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2007 Jan;59(1):139-47. Epub 2006 Jul 4. PubMed PMID: 16819636.

10: Ciomei M, Croci V, Ciavolella A, Ballinari D, Pesenti E. Antitumor efficacy of edotecarin as a single agent and in combination with chemotherapy agents in a xenograft model. Clin Cancer Res. 2006 May 1;12(9):2856-61. PubMed PMID: 16675581.

11: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Mar;28(2):121-42. PubMed PMID: 16636723.

12: Vrdoljak E, Boban M, Saratlija-Novaković Z, Jović J. Long-lasting partial regression of glioblastoma multiforme achieved by edotecarin: case report. Croat Med J. 2006 Apr;47(2):305-9. PubMed PMID: 16625697; PubMed Central PMCID: PMC2080410.

13: Yamada Y, Tamura T, Yamamoto N, Shimoyama T, Ueda Y, Murakami H, Kusaba H, Kamiya Y, Saka H, Tanigawara Y, McGovren JP, Natsumeda Y. Phase I and pharmacokinetic study of edotecarin, a novel topoisomerase I inhibitor, administered once every 3 weeks in patients with solid tumors. Cancer Chemother Pharmacol. 2006 Aug;58(2):173-82. Epub 2005 Nov 25. PubMed PMID: 16308697.

14: Saif MW, Diasio RB. Edotecarin: a novel topoisomerase I inhibitor. Clin Colorectal Cancer. 2005 May;5(1):27-36. Review. PubMed PMID: 15929804.

15: O'Neil BH, Goldberg RM. Chemotherapy for advanced colorectal cancer: let's not forget how we got here (until we really can). Semin Oncol. 2005 Feb;32(1):35-42. Review. PubMed PMID: 15726504.

16: Denny WA. Edotecarin. IDrugs. 2004 Feb;7(2):173-7. PubMed PMID: 15057663.

17: Cavazos CM, Keir ST, Yoshinari T, Bigner DD, Friedman HS. Therapeutic activity of the topoisomerase I inhibitor J-107088 [6-N-(1-hydroxymethyla-2-hydroxyl) ethylamino-12,13-dihydro-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7(6H)-dione]] against pediatric and adult central nervous system tumor xenografts. Cancer Chemother Pharmacol. 2001 Sep;48(3):250-4. PubMed PMID: 11592348.

18: Komatani H, Kotani H, Hara Y, Nakagawa R, Matsumoto M, Arakawa H, Nishimura S. Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res. 2001 Apr 1;61(7):2827-32. PubMed PMID: 11306452.

19: Ohkubo M, Nishimura T, Kawamoto H, Nakano M, Honma T, Yoshinari T, Arakawa H, Suda H, Morishima H, Nishimura S. Synthesis and biological activities of NB-506 analogues modified at the glucose group. Bioorg Med Chem Lett. 2000 Mar 6;10(5):419-22. PubMed PMID: 10743939.

20: Arakawa H, Morita M, Kodera T, Okura A, Ohkubo M, Morishima H, Nishimura S. In vivo anti-tumor activity of a novel indolocarbazole compound, J-107088, on murine and human tumors transplanted into mice. Jpn J Cancer Res. 1999 Oct;90(10):1163-70. PubMed PMID: 10595746.

21: Yoshinari T, Ohkubo M, Fukasawa K, Egashira S, Hara Y, Matsumoto M, Nakai K, Arakawa H, Morishima H, Nishimura S. Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I. Cancer Res. 1999 Sep 1;59(17):4271-5. PubMed PMID: 10485471.