Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma.
Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma.
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DOI：
10.1021/acs.jmedchem.0c00225
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发表时间：
2020-07-09
影响因子：
7.3
通讯作者：
Minor W
中科院分区：
文献类型：
--
作者：
Czub MP;Handing KB;Venkataramany BS;Cooper DR;Shabalin IG;Minor W
每天，全世界有数亿人服用非甾体抗炎药（NSAID），通常与多种其他药物联合使用。在血液中，NSAID主要与血清白蛋白（SA）结合。我们报告了马血清白蛋白与四种非甾体抗炎药（布洛芬、酮洛芬、依托度酸和萘丁美酮）和萘丁美酮的活性代谢物（6-甲氧基-2-萘乙酸，6-MNA）复合的晶体结构。这些化合物与SA上的七个药物结合位点结合。这些位点在马和人SA之间通常是很保守的，但布洛芬在两个药物结合位点与两个SA结合，其中只有一个是共同的。我们还比较了酮洛芬的马SA的结合，它的结合牛和兔SA。我们对已知的SA复合物与FDA批准的药物的比较分析清楚地表明，多种药物竞争相同的结合位点，这表明药物-药物置换或与常见代谢物竞争可能引起不良生理效应。我们讨论的后果，非甾体抗炎药结合SA在更广泛的科学和医学背景下，特别是关于实现所需的治疗效果的基础上，个人的药物治疗方案。
Every day, hundreds of millions of people worldwide take nonsteroidal anti-inflammatory drugs (NSAIDs), often in conjunction with multiple other medications. In the bloodstream, NSAIDs are mostly bound to serum albumin (SA). We report the crystal structures of equine serum albumin complexed with four NSAIDs (ibuprofen, ketoprofen, etodolac, and nabumetone) and the active metabolite of nabumetone (6-methoxy-2-naphthylacetic acid, 6-MNA). These compounds bind to seven drug-binding sites on SA. These sites are generally well-conserved between equine and human SAs, but ibuprofen binds to both SAs in two drug-binding sites, only one of which is common. We also compare the binding of ketoprofen by equine SA to binding of it by bovine and leporine SAs. Our comparative analysis of known SA complexes with FDA-approved drugs clearly shows that multiple medications compete for the same binding sites, indicating possibilities for undesirable physiological effects caused by drug–drug displacement or competition with common metabolites. We discuss the consequences of NSAID binding to SA in a broader scientific and medical context, particularly regarding achieving desired therapeutic effects based on an individual’s drug regimen.
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DOI：
10.1016/j.str.2017.10.009
发表时间：
2017-12-05
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Gore S;Sanz García E;Hendrickx PMS;Gutmanas A;Westbrook JD;Yang H;Feng Z;Baskaran K;Berrisford JM;Hudson BP;Ikegawa Y;Kobayashi N;Lawson CL;Mading S;Mak L;Mukhopadhyay A;Oldfield TJ;Patwardhan A;Peisach E;Sahni G;Sekharan MR;Sen S;Shao C;Smart OS;Ulrich EL;Yamashita R;Quesada M;Young JY;Nakamura H;Markley JL;Berman HM;Burley SK;Velankar S;Kleywegt GJ
通讯作者：
Kleywegt GJ
影响因子：
12.4
作者：
An FF;Zhang XH
通讯作者：
Zhang XH
DOI：
10.1016/j.cca.2013.07.013
发表时间：
2013-10-21
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
--
作者：
Anguizola J;Matsuda R;Barnaby OS;Hoy KS;Wa C;DeBolt E;Koke M;Hage DS
通讯作者：
Hage DS
影响因子：
3.4
作者：
Evans, AM
通讯作者：
Evans, AM
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K