A framework for assessing the risk of resistance for anti-malarials in development.
A framework for assessing the risk of resistance for anti-malarials in development.
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DOI：
10.1186/1475-2875-11-292
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发表时间：
2012-08-22
期刊：
影响因子：
3
通讯作者：
Wells TN
中科院分区：
文献类型：
--
作者：
Ding XC;Ubben D;Wells TN
耐药性是抗感染药物开发的持续挑战。由于抗感染剂会杀死敏感生物体，因此如果随机突变事件可以产生这种耐药性，那么它们必然会对耐药机制的出现和传播施加进化压力。必须设计或选择正在开发的新型药物，以在耐药性控制的恶性循环中保持领先地位。这既涉及规避现有的耐药机制，又涉及选择能够抵抗耐药性发展和传播的分子。基于细胞的筛选方法导致了新型抗疟疾药物的复兴，使我们有可能根据分子的耐药潜力来选择和修饰分子。为此，我们开发了一种标准化的体外方法，用于在药物开发过程的早期阶段定量评估恶性疟原虫的这些特征，并在此介绍。它可以识别具有明显耐药风险的抗疟化合物，并优先考虑最有效的化合物。还讨论了该策略在开发、注册和部署后期阶段的集成。
Resistance is a constant challenge for anti-infective drug development. Since they kill sensitive organisms, anti-infective agents are bound to exert an evolutionary pressure toward the emergence and spread of resistance mechanisms, if such resistance can arise by stochastic mutation events. New classes of medicines under development must be designed or selected to stay ahead in this vicious circle of resistance control. This involves both circumventing existing resistance mechanisms and selecting molecules which are resilient against the development and spread of resistance. Cell-based screening methods have led to a renaissance of new classes of anti-malarial medicines, offering us the potential to select and modify molecules based on their resistance potential. To that end, a standardized in vitro methodology to assess quantitatively these characteristics in Plasmodium falciparum during the early phases of the drug development process has been developed and is presented here. It allows the identification of anti-malarial compounds with overt resistance risks and the prioritization of the most robust ones. The integration of this strategy in later stages of development, registration, and deployment is also discussed.
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DOI：
10.1083/jcb.135.1.269
发表时间：
1996-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Guinet F;Dvorak JA;Fujioka H;Keister DB;Muratova O;Kaslow DC;Aikawa M;Vaidya AB;Wellems TE
通讯作者：
Wellems TE
影响因子：
15.8
作者：
Delves M;Plouffe D;Scheurer C;Meister S;Wittlin S;Winzeler EA;Sinden RE;Leroy D
通讯作者：
Leroy D
影响因子：
12.3
作者：
Dharia NV;Sidhu AB;Cassera MB;Westenberger SJ;Bopp SE;Eastman RT;Plouffe D;Batalov S;Park DJ;Volkman SK;Wirth DF;Zhou Y;Fidock DA;Winzeler EA
通讯作者：
Winzeler EA
影响因子：
4.2
作者：
Burrows, Jeremy N.;Leroy, Didier;Waterson, David
通讯作者：
Waterson, David
DOI：
10.1073/pnas.1011560108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Istvan, Eva S.;Dharia, Neekesh V.;Goldberg, Daniel E.
通讯作者：
Goldberg, Daniel E.