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[摘要]：Acadesine (AICA-riboside, Acadra (R)) is a well-known small molecule produced by either chemical synthesis or bacterial fermentation. It has undergone extensive clinical development for cardiovascular disorders but never reached the market for these indications due to efficacy concerns. The drug has shown anticancer activity in a wide panel of in vitro and in vivo models of B-cell hematological malignances, without affecting T cells. In these indications, acadesine has a novel mechanism of action mediated by nucleotide pool disruption and which is independent of p53 status, making it effective in B cells resistant to p53-dependent therapies. Acadesine was recently shown to have a predictable and good safety profile at doses associated with antitumor activity in a phase IIa clinical study in chronic lymphocytic leukemia (CLL) patients. Acadesine is undergoing phase II development for the treatment of several B-cell hematological malignances, including CLL, multiple myeloma, mantle cell lymphoma and acute lymphoblostic leukemia. |
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