Amonafide produces protein-associated DNA-strand breaks through atopoisomerase II-mediated reaction, but does not producetopoisomerase I-mediated DNA cleavage.
Topoisomerase II (topo II) is an enzyme essential for chromosome segregation and DNA supercoiling homeostasis[3]. Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA[4]. In vitro, P-glycoprotein (Pgp)-mediated transport (efflux) of amonafide from myeloblasts obtained from patients with secondary acute myeloid leukemia (sAML) was significantly less than efflux of daunorubicin[4]. Amonafide produces protein-associated DNA cleavage, single-strand breaks (SSB) and DPC and DNA double-strand cleavage. Amonafide (400 nM-2.4 μM) reduces the colony-forming ability of the leukemic cell lines in a dose-dependent manner[5]. Amonafide has shown efficacy in patients with sAML, as well as in patients with poor prognostic characteristics such as older age and unfavorable cytogenetics, all associated with drug resistance (MDR). Improved antileukemic activity is observed when amonafide is given together with cytarabine, rather than as monotherapy, with a complete remission rate of ∼ 40% in a recent Phase II trial in sAML[4].
United States, California
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USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Maryland
Cancer Center at John Hopkins
Baltimore, Maryland, United States, 21231
United States, Missouri
Barnard Cancer Center
St.Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
Herbert Irving Cancer Center
New York, New York, United States, 10032-3789
United States, Ohio
The Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109 收起 <<
United States, California
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USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Maryland
Cancer Center at John Hopkins
Baltimore, Maryland, United States, 21231
United States, Missouri
Barnard Cancer Center
St.Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
Herbert Irving Cancer Center
New York, New York, United States, 10032-3789
United States, Ohio
The Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109 收起 <<
Georgia
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Tbilisi, Georgia, 0177
Medulla - Chemotherapy and Immunotherapy Clinic
Tbilisi, Georgia, 0186
Hema - Haematology and Chemotherapy Clinic
Tbilisi, Georgia
Ukraine
Institure of URgent adn Recovery Surgery n.a. V.K. gusaka of Academy Medical Science of Ukraine
Donetsk, Ukraine, 83045
Kyiv bone Marrow Transplantation Centre
Kiev, Ukraine, 03115
Vinnytsya Regional clinical Hospital
Vinnytsya, Ukraine, 21018 收起 <<
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