Advances in Chagas disease drug development: 2009-2010.
Advances in Chagas disease drug development: 2009-2010.
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DOI：
10.1097/qco.0b013e3283402956
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发表时间：
2010-12
影响因子：
3.9
通讯作者：
Navabi N
中科院分区：
文献类型：
--
作者：
Buckner FS;Navabi N
The need for better drugs to treat patients with Chagas disease remains urgent. This review summarizes the advancements in drug development over the past two years. Drug development efforts are almost exclusively occurring as preclinical research. The exceptions being Phase I safety studies for the cruzain inhibitor, K-777, and potential Phase II studies for the antifungal drug, posaconazole, and a prodrug of ravuconazole. Several recent laboratory investigations demonstrate anti-T. cruzi activity of novel small molecules in animal models. These include nonpeptidic cruzain inhibitors, novel inhibitors of the sterol 14α-demethylase enzyme, new compounds (arylimidamides) related to pentamidine, derivatives of nifurtimox, compounds using ruthenium complexes, and several natural products. The recent implementation of a high-throughput screen of >300,000 compounds against intracellular T. cruzi amastigotes done at the Broad Institute is an important development, yielding ~300 selective inhibitors, many of which may serve as leads for medicinal chemistry efforts. Progress is slow, but recent advancements in both drug development and advocacy for research on neglected diseases are encouraging. Efforts to define a target product profile and to harmonize methodologies for testing drugs for Chagas disease are described herein.
