Practical Considerations For Developing Nucleoside Reverse Transcriptase Inhibitors.
Practical Considerations For Developing Nucleoside Reverse Transcriptase Inhibitors.
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DOI：
10.1016/j.ddtec.2012.09.003
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Schinazi RF
中科院分区：
文献类型：
--
作者：
Hurwitz SJ;Schinazi RF
核苷类逆转录酶抑制剂（NRTI）仍然是目前抗逆转录病毒治疗方案的基石，通常与非核苷类逆转录酶抑制剂（NNRTI）、蛋白酶抑制剂（PI）或整合酶抑制剂（INI）联合使用。目前NRTI的抗逆转录病毒疗效和相对安全性来自其磷酸化核苷三磷酸（NRTI-TP）与HIV-1逆转录酶的紧密和相对特异性结合，这是复制所必需的。NRTI-TP的细胞内稳定性产生持续的抗病毒应答，这使得方便的给药变得可行。关于NRTI药理学筛选，开发和使用的经验教训进行了讨论。概述了目前正在临床开发的NRTI和前药。
Nucleoside reverse transcriptase inhibitors (NRTI) remain a cornerstone of current antiretroviral regimens in combinations usually with a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase inhibitor (INI). The antiretroviral efficacy and relative safety of current NRTI results from a tight and relatively specific binding of their phosphorylated nucleoside triphosphates (NRTI-TP) with the HIV-1 reverse transcriptase which is essential for replication. The intracellular stability of NRTI-TP produces a sustained antiviral response, which makes convenient dosing feasible. Lessons learned regarding NRTI pharmacology screening, development, and use are discussed. NRTI and prodrugs currently under clinical development are outlined.