Borchmann Peter, Schnell Roland
University of Cologne, 1st Department of Internal Medicine, Cologne, Germany.
Expert Opin Investig Drugs. 2005 Aug;14(8):1055-61. doi: 10.1517/13543784.14.8.1055.
Pixantrone is an anthraquinone-based inhibitor of topoisomerase II. It is similar to both the anthracycline doxorubicin and the anthracenedione mitoxantrone, but lacks the 5,8-dihydroxy substitution pattern of mitoxantrone, and has a tricyclic system unlike the tetracyclic structure seen with anthracyclines. Anthracyclines are the most active drugs in lymphoma therapy, but their use is limited by their cumulative and irreversible cardiotoxicity. Pixantrone was developed to improve the toxicity profile of the current anthracyclines and anthracenediones while maintaining their activity. Interestingly, pixantrone showed no measurable cardiotoxicity compared with its parent compound mitoxantrone or other anthracyclines at equi-effective doses in several animal models. Together with its superior cytotoxic activity in leukaemia and lymphoma models, these features render the drug a promising candidate for clinical development in indolent and aggressive non-Hodgkin's lymphoma. In this review, the latest results of the use of pixantrone in indolen-t and aggressive non-Hodgkin's lymphomas are summarised.
匹杉琼是一种基于蒽醌的拓扑异构酶II抑制剂。它与蒽环类药物阿霉素和蒽二酮米托蒽醌都相似，但缺乏米托蒽醌的5,8 - 二羟基取代模式，并且具有三环系统，这与蒽环类药物的四环结构不同。蒽环类药物是淋巴瘤治疗中最有效的药物，但其使用受到累积性和不可逆心脏毒性的限制。开发匹杉琼是为了在保持当前蒽环类药物和蒽二酮活性的同时改善其毒性特征。有趣的是，在几种动物模型中，与等效剂量的母体化合物米托蒽醌或其他蒽环类药物相比，匹杉琼未显示出可测量的心脏毒性。连同其在白血病和淋巴瘤模型中卓越的细胞毒性活性，这些特性使该药物成为惰性和侵袭性非霍奇金淋巴瘤临床开发的有希望的候选药物。在这篇综述中，总结了匹杉琼用于惰性和侵袭性非霍奇金淋巴瘤的最新结果。
