A Biological Basis for Pharmacokinetics: The Remote Sensing and Signaling Theory.

A Biological Basis for Pharmacokinetics: The Remote Sensing and Signaling Theory.
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DOI:
10.1002/cpt.2634
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发表时间:
2022-09
影响因子:
6.7
通讯作者:
Granados, Jeffry C.
Granados, Jeffry C.
中科院分区:
医学2区
文献类型:
--
作者:
Nigam, Sanjay K.;Granados, Jeffry C.

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药物转运蛋白和药物代谢酶(DME)-以及参与药物吸收,分布,代谢和排泄(ADME)的各种调节蛋白-真正做什么(1)?对于那些来自非制药背景的人来说,这似乎是一个非常合理的问题,如果不是紧迫的话。他们到底做什么?它们真正的生物学功能是什么?为了理解这一点,我们必须超越经典的多特异性“药物”转运蛋白和“药物”代谢酶(2,3)。我们必须考虑寡特异性和单特异性转运蛋白,酶和调节蛋白(例如,核受体,激酶),他们经常工作-在药代动力学和内源性代谢的背景下。蛋白质的列表相当大;粗略估计为500-1000(4)。换句话说,也许多达5%的人类基因组致力于处理与许多药物具有分子相似性的内源性小分子。
What do drug transporters and drug metabolizing enzymes (DMEs)--as well as the various regulatory proteins involved in the absorption, distribution, metabolism and excretion (ADME) of drugs--really do (1)? To those coming from a non-pharmaceutical background, this seems a very reasonable, if not urgent, question. What do they really do? What is their true biological function?To understand this, we must go beyond the classic multi-specific “drug” transporters and “drug” metabolizing enzymes (2, 3). We must consider the oligo-specific and mono-specific transporters, enzymes and regulatory proteins (eg, nuclear receptors, kinases) they often work with--in the contexts of both pharmacokinetics and endogenous metabolism. The list of proteins is quite large; a rough estimate is 500–1000 (4). In other words, perhaps as much as 5% of the human genome is dedicated to handling endogenous small molecules that bear a molecular resemblance to numerous pharmaceuticals.
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