Carboxylesterase inhibitors.
Carboxylesterase inhibitors.
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DOI：
10.1517/13543776.2011.586339
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发表时间：
2011-08
影响因子：
6.6
通讯作者：
Potter PM
中科院分区：
文献类型：
--
作者：
Hatfield MJ;Potter PM
羧酸酯酶在许多治疗活性化合物的水解中起主要作用。这部分是由于这些小分子中酯部分的普遍存在。然而，这些酶可能对药物稳定性和药代动力学的影响在分子开发之前很少被考虑。因此，这类蛋白质的选择性抑制剂的应用可用于调节经受酶水解的试剂的代谢、分布和毒性。本文详细介绍了所有这些化合物的发展可追溯到1986年，但主要集中在最近确定的选择性人类羧酸酯酶抑制剂。羧酸酯酶抑制剂的应用可能会使药物发现发生重大变革。这样的分子可以允许由这类酶灭活的化合物的改善的功效和/或降低由这些蛋白质活化的试剂的毒性。此外，由于缺乏羧酸酯酶活性似乎没有明显的生物学后果，这些化合物可以与几乎任何酯化药物组合使用。因此，这些蛋白质的抑制剂可能具有改变药物水解和体内分布的效用。本文讨论了这类制剂的特点、化学和生物学性质及其潜在用途。
Carboxylesterases play major roles in the hydrolysis of numerous therapeutically active compounds. This is, in part, due to the prevalence of the ester moiety in these small molecules. However, the impact these enzymes may play on drug stability and pharmacokinetics is rarely considered prior to molecule development. Therefore, the application of selective inhibitors of this class of proteins may have utility in modulating the metabolism, distribution and toxicity of agents that are subjected to enzyme hydrolysis. This review details the development of all such compounds dating back to 1986, but principally focuses on the very recent identification of selective human carboxylesterases inhibitors. The implementation of carboxylesterase inhibitors may significantly revolutionize drug discovery. Such molecules may allow for improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these proteins. Furthermore, since lack of carboxylesterase activity appears to have no obvious biological consequence, these compounds could be applied in combination with virtually any esterified drug. Therefore, inhibitors of these proteins may have utility in altering drug hydrolysis and distribution in vivo. The characteristics, chemical and biological properties, and potential uses of such agents, are discussed here.
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影响因子：
2.9
作者：
GELB, MH;SVAREN, JP;ABELES, RH
通讯作者：
ABELES, RH
DOI：
10.1016/j.bbalip.2009.09.002
发表时间：
2010-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Crow JA;Herring KL;Xie S;Borazjani A;Potter PM;Ross MK
通讯作者：
Ross MK
影响因子：
5.6
作者：
Fleming, CD;Bencharit, S;Redinbo, MR
通讯作者：
Redinbo, MR
影响因子：
5.6
作者：
Bencharit, Sompop;Edwards, Carol C.;Redinbo, Matthew R.
通讯作者：
Redinbo, Matthew R.
影响因子：
3.9
作者：
Alexson, SEH;Diczfalusy, M;Swedmark, S
通讯作者：
Swedmark, S