Adozelesin, a selected lead among cyclopropylpyrroloindole analogs of the DNA-binding antibiotic, CC-1065
Autor: | Thomas F. DeKoning, I. Gebhard, Kelly Robert C, J. Patrick McGovren, L. H. Li, Martha A. Warpehoski |
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Rok vydání: | 1991 |
Předmět: |
Male
Indoles Lung Neoplasms Cyclohexanecarboxylic Acids Melanoma Experimental Mice Nude Antineoplastic Agents Duocarmycins Mice In vivo Cyclohexenes Carcinoma Animals Humans Medicine Pharmacology (medical) Doxorubicin Leukemia L1210 Benzofurans Pharmacology Cisplatin Leukemia Experimental Molecular Structure business.industry Lewis lung carcinoma DNA Neoplasm medicine.disease Pancreatic Neoplasms Oncology Adozelesin Colonic Neoplasms Immunology Cancer research Adenocarcinoma Female Sarcoma Experimental Sarcoma business Neoplasm Transplantation medicine.drug |
Zdroj: | Investigational New Drugs. 9:137-148 |
ISSN: | 1573-0646 0167-6997 |
Popis: | Adozelesin (U-73975) is a potent synthetic cyclopropylpyrroloindole (CPI) analog of the cytotoxic DNA-binding antibiotic, CC-1065. In contrast to the natural product, adozelesin and related CPI analogs do not cause delayed death in non-tumored mice. Adozelesin, selected from a series of analogs for its superior in vivo antitumor activity and ease of formulation, is highly active when administered i.v. against i.p. - or s.c.- implanted murine tumors, including L1210 leukemia, B16 melanoma, M5076 sarcoma, and colon 38 carcinoma, and produces long-term survivors in mice bearing i.v.-inoculated L1210 and Lewis lung carcinoma. Modest activity is shown against the highly drug-resistant pancreas 02 carcinoma. Adozelesin is also highly effective against human tumor xenografts s.c.-implanted in athymic (nude) mice, including colon CX-1 adenocarcinoma, lung LX-1 tumor, clear cell Caki-1 carcinoma, and ovarian 2780 carcinoma. Its broad spectrum of in vivo activity compares favorably with three widely used antitumor drugs, i.e. cisplatin, cyclophosphamide, and doxorubicin. Adozelesin appears to be more effective than these drugs in the treatment of very resistant tumors such as s.c.-implanted mouse B16 melanoma, pancreatic 02 carcinoma, and human colon CX-1 and human lung LX-1 tumor xenografts. Based on its high potency and high efficacy against a broad spectrum of experimental tumors, adozelesin was chosen for clinical investigation and development. |
Databáze: | OpenAIRE |
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