E-3174 (BioDeep_00000010771)

 

Secondary id: BioDeep_00000404843

human metabolite Endogenous blood metabolite


代谢物信息卡片


2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazole-5-carboxylic acid

化学式: C22H21ClN6O2 (436.1414436)
中文名称: 氯沙坦
谱图信息: 最多检出来源 Homo sapiens(blood) 7.87%

分子结构信息

SMILES: CCCCC1=NC(=C(N1CC2=CC=C(C=C2)C3=CC=CC=C3C4=NNN=N4)C(=O)O)Cl
InChI: InChI=1S/C22H21ClN6O2/c1-2-3-8-18-24-20(23)19(22(30)31)29(18)13-14-9-11-15(12-10-14)16-6-4-5-7-17(16)21-25-27-28-26-21/h4-7,9-12H,2-3,8,13H2,1H3,(H,30,31)(H,25,26,27,28)

描述信息

EXP3174 is a metabolite of losartan (previous name DuP753), which is a non-peptide angiotensin II receptor antagonist. EXP3174, a metabolite of losartan (MK 954, DuP 753) is more potent than losartan in blocking the angiotensin II-induced responses in vascular smooth muscle cells. (PMID: 8385175)
D002317 - Cardiovascular Agents > D000959 - Antihypertensive Agents
D002317 - Cardiovascular Agents > D000889 - Anti-Arrhythmia Agents
Losartan Carboxylic Acid (E-3174), an active carboxylic acid metabolite of Losartan, is an angiotensin II receptor type 1 (AT1) antagonist. The Ki values are 0.97, 0.57, 0.67 nM for rat AT1B/AT1A and human AT1, respectively. Losartan Carboxylic Acid blocks the angiotensin II-induced responses in vascular smoothmuscle cells (VSMC). Losartan Carboxylic Acid elevates plasma renin activities and reduces mean arterial pressure[1][2][3][4].

同义名列表

10 个代谢物同义名

2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazole-5-carboxylic acid; 2-butyl-5-chloro-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)imidazole-4-carboxylic acid; 2-N-Butyl-4-chloro-1-((2-(1H-tetrazol-5-yl)biphenyl-4-yl)methylll)imidazole-5-carboxylic acid; Losartan Metabolite (E 3174); Losartan carboxylic acid; Losartan carboxylate; EXP 3174; E-3174; EXP-3174; EXP 3174



数据库引用编号

13 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(0)

BioCyc(0)

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代谢反应

0 个相关的代谢反应过程信息。

Reactome(0)

BioCyc(0)

WikiPathways(0)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

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PharmGKB(0)

1 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。



文献列表

  • Rui Li, Chuanzhou Liang, Sif B Svendsen, Vaidotas Kisielius, Kai Bester. Sartan blood pressure regulators in classical and biofilm wastewater treatment - Concentrations and metabolism. Water research. 2023 Feb; 229(?):119352. doi: 10.1016/j.watres.2022.119352. [PMID: 36450176]
  • Eleni Karatza, Vangelis Karalis. Modelling gastric emptying: A pharmacokinetic model simultaneously describing distribution of losartan and its active metabolite EXP-3174. Basic & clinical pharmacology & toxicology. 2020 Mar; 126(3):193-202. doi: 10.1111/bcpt.13321. [PMID: 31514255]
  • Xiuli Li, Jingchao Sun, Zitao Guo, Dafang Zhong, Xiaoyan Chen. Carboxylesterase 2 and Intestine Transporters Contribute to the Low Bioavailability of Allisartan, a Prodrug of Exp3174 for Hypertension Treatment in Humans. Drug metabolism and disposition: the biological fate of chemicals. 2019 08; 47(8):843-853. doi: 10.1124/dmd.118.085092. [PMID: 31076412]
  • A Gromotowicz-Poplawska, J Nazarko-Sadowska, E Chabielska. Losartan metabolite EXP3174 reduces the weight of formed thrombus in 2K1C hypertensive rats. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2019 Jun; 70(3):. doi: 10.26402/jpp.2019.3.11. [PMID: 31566190]
  • Qingling Zhao, Jinlan Wei, Hongying Zhang. Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. Xenobiotica; the fate of foreign compounds in biological systems. 2019 May; 49(5):563-568. doi: 10.1080/00498254.2018.1478168. [PMID: 29768080]
  • Baiping Dong, Suowei Yuan, Jinsheng Hu, Yanzhen Yan. Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism. Pharmaceutical biology. 2018 Dec; 56(1):333-336. doi: 10.1080/13880209.2018.1481107. [PMID: 29953302]
  • Ying Zhang, Lan Miao, Li Lin, Chang-Ying Ren, Jian-Xun Liu, Yi-Min Cui. Repeated administration of Sailuotong, a fixed combination of Panax ginseng, Ginkgo biloba, and Crocus sativus extracts for vascular dementia, alters CYP450 activities in rats. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018 Jan; 38(?):125-134. doi: 10.1016/j.phymed.2017.02.007. [PMID: 29425645]
  • Yongsheng Hu, Xuexue Zhou, Hui Shi, Wenyu Shi, Shengjie Ye, Hai Zhang. The effect of tripterygium glucoside tablet on pharmacokinetics of losartan and its metabolite EXP3174 in rats. Biomedical chromatography : BMC. 2017 Oct; 31(10):. doi: 10.1002/bmc.3973. [PMID: 28299812]
  • Hoa Q Nguyen, Jian Lin, Emi Kimoto, Ernesto Callegari, Susanna Tse, R Scott Obach. Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically Based Pharmacokinetic Models. Journal of pharmaceutical sciences. 2017 09; 106(9):2758-2770. doi: 10.1016/j.xphs.2017.03.032. [PMID: 28412400]
  • Hong Li, Lu Liu, Lei Xie, Dongmei Gan, Xiaoqing Jiang. Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism. Pharmaceutical biology. 2016 Dec; 54(12):2886-2894. doi: 10.1080/13880209.2016.1190762. [PMID: 27327872]
  • Robert Hennig, Andreas Ohlmann, Janina Staffel, Klaus Pollinger, Alexandra Haunberger, Miriam Breunig, Frank Schweda, Ernst R Tamm, Achim Goepferich. Multivalent nanoparticles bind the retinal and choroidal vasculature. Journal of controlled release : official journal of the Controlled Release Society. 2015 Dec; 220(Pt A):265-274. doi: 10.1016/j.jconrel.2015.10.033. [PMID: 26494258]
  • Basma Ismail, Tayebeh Hadizad, Rawad Antoun, Mireille Lortie, Robert A deKemp, Rob S B Beanlands, Jean N DaSilva. Evaluation of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 for PET imaging of renal AT1receptor in rats. Nuclear medicine and biology. 2015 Nov; 42(11):850-7. doi: 10.1016/j.nucmedbio.2015.06.012. [PMID: 26300209]
  • Mustafa Tugrul Goktaş, Fazleen Hatta, Ozgur Karaca, Said Kalkisim, Levent Kilic, Ali Akdogan, Melih O Babaoglu, Atilla Bozkurt, Anders Helldén, Leif Bertilsson, Umit Yasar. Lower CYP2C9 activity in Turkish patients with Behçet's disease compared to healthy subjects: a down-regulation due to inflammation?. European journal of clinical pharmacology. 2015 Oct; 71(10):1223-8. doi: 10.1007/s00228-015-1899-7. [PMID: 26233334]
  • Sung Ha Ryu, Yong Soon Kim, Hyun-Jun Jang, Kyu-Bong Kim. Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats. Journal of toxicology and environmental health. Part A. 2015; 78(20):1299-309. doi: 10.1080/15287394.2015.1085355. [PMID: 26514876]
  • C Lv, C Wei, X Wang, H Yao, R Li, B Wang, R Guo. The influence of food on the pharmacokinetics of amlodipine and losartan after single-dose of its compound tablets in healthy chinese subjects. Drug research. 2014 May; 64(5):229-35. doi: 10.1055/s-0033-1357143. [PMID: 24132705]
  • Yongfang Yuan, Hai Zhang, Weina Ma, Sen Sun, Benwei Wang, Liang Zhao, Guoqing Zhang, Yifeng Chai. Influence of compound danshen tablet on the pharmacokinetics of losartan and its metabolite EXP3174 by liquid chromatography coupled with mass spectrometry. Biomedical chromatography : BMC. 2013 Sep; 27(9):1219-24. doi: 10.1002/bmc.2930. [PMID: 23722257]
  • M Spanakis, I S Vizirianakis, G Batzias, I Niopas. Pharmacokinetic interaction between losartan and Rhodiola rosea in rabbits. Pharmacology. 2013; 91(1-2):112-6. doi: 10.1159/000345929. [PMID: 23327826]
  • S M Arslanbekova, D A Sychev, R E Kazakov, V V Smirnov, E V Kuznetsova, E Z Golukhova. [Relationship between warfarin dosing and activity of CYP2C9 assessed by the content of losartan and its metabolite E-3174 in the urine of patients with mechanical prosthetic heart valves]. Kardiologiia. 2013; 53(12):21-4. doi: NULL. [PMID: 24800477]
  • Jung-Woo Bae, Chang-Ik Choi, Hye-In Lee, Yun-Jeong Lee, Choon-Gon Jang, Seok-Yong Lee. Effects of CYP2C9*1/*3 and *1/*13 on the pharmacokinetics of losartan and its active metabolite E-3174. International journal of clinical pharmacology and therapeutics. 2012 Sep; 50(9):683-9. doi: 10.5414/cp201467. [PMID: 22735459]
  • Kyung-Suk Oh, Su-Jin Park, Dhananjay D Shinde, Jae-Gook Shin, Dong-Hyun Kim. High-sensitivity liquid chromatography-tandem mass spectrometry for the simultaneous determination of five drugs and their cytochrome P450-specific probe metabolites in human plasma. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2012 May; 895-896(?):56-64. doi: 10.1016/j.jchromb.2012.03.014. [PMID: 22483397]
  • L Yang, T Guo, D-Y Xia, L-S Zhao. Pharmacokinetics of losartan and its active carboxylic acid metabolite E-3174 in five ethnic populations of China. Journal of clinical pharmacy and therapeutics. 2012 Apr; 37(2):226-31. doi: 10.1111/j.1365-2710.2011.01279.x. [PMID: 21777404]
  • An-Chang Liu, Li-Xia Zhao, Jie Xing, Tian Liu, Fu-Ying Du, Hong-Xiang Lou. Pre-treatment with curcumin enhances plasma concentrations of losartan and its metabolite EXP3174 in rats. Biological & pharmaceutical bulletin. 2012; 35(2):145-50. doi: 10.1248/bpb.35.145. [PMID: 22293343]
  • Pedro Dorado, Esther Machín, Fernando de Andrés, María-Eugenia Naranjo, Eva M Peñas-Lledó, Adrián Llerena. Development of a HPLC method for the determination of losartan urinary metabolic ratio to be used for the determination of CYP2C9 hydroxylation phenotypes. Drug metabolism and drug interactions. 2012; 27(4):217-33. doi: 10.1515/dmdi-2012-0018. [PMID: 23093260]
  • Si-hyung Yang, Young-ah Cho, Jun-shik Choi. Effects of ticlopidine on pharmacokinetics of losartan and its main metabolite EXP-3174 in rats. Acta pharmacologica Sinica. 2011 Jul; 32(7):967-72. doi: 10.1038/aps.2011.32. [PMID: 21666702]
  • Si-Hyung Yang, Jun-Shik Choi, Dong-Hyun Choi. Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of losartan and its main metabolite EXP-3174 in rats: possible role of CYP3A4 and P-gp inhibition by HMG-CoA reductase inhibitors. Pharmacology. 2011; 88(1-2):1-9. doi: 10.1159/000328773. [PMID: 21709429]
  • Yi-Dong Yan, Han-Kyung Kim, Ki-Heon Seo, Won Seok Lee, Gwan-Sun Lee, Jong-Soo Woo, Chul-Soon Yong, Han-Gon Choi. The physicochemical properties, in vitro metabolism and pharmacokinetics of a novel ester prodrug of EXP3174. Molecular pharmaceutics. 2010 Dec; 7(6):2132-40. doi: 10.1021/mp100166c. [PMID: 20849146]
  • Dong-Hyun Choi, Cheng Li, Jun-Shik Choi. Effects of myricetin, an antioxidant, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats: possible role of cytochrome P450 3A4, cytochrome P450 2C9 and P-glycoprotein inhibition by myricetin. The Journal of pharmacy and pharmacology. 2010 Jul; 62(7):908-14. doi: 10.1211/jpp.62.07.0012. [PMID: 20636879]
  • Masayuki Tsujimoto, Keishi Higuchi, Daisuke Shima, Hitoshi Yokota, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Masaki Otagiri, Sumio Hirata, Kohji Takara, Kohshi Nishiguchi. Inhibitory effects of uraemic toxins 3-indoxyl sulfate and p-cresol on losartan metabolism in vitro. The Journal of pharmacy and pharmacology. 2010 Jan; 62(1):133-8. doi: 10.1211/jpp.62.01.0015. [PMID: 20723009]
  • Ana Fortuño, Julen Bidegain, Pablo A Robador, José Hermida, Jacinto López-Sagaseta, Oscar Beloqui, Javier Díez, Guillermo Zalba. Losartan metabolite EXP3179 blocks NADPH oxidase-mediated superoxide production by inhibiting protein kinase C: potential clinical implications in hypertension. Hypertension (Dallas, Tex. : 1979). 2009 Oct; 54(4):744-50. doi: 10.1161/hypertensionaha.109.129353. [PMID: 19687351]
  • Kai Kappert, Oleg Tsuprykov, Jan Kaufmann, Jan Fritzsche, Ingo Ott, Matthias Goebel, Ilse Nirmala Bähr, Paul-Laszlo Hässle, Ronald Gust, Eckart Fleck, Thomas Unger, Philipp Stawowy, Ulrich Kintscher. Chronic treatment with losartan results in sufficient serum levels of the metabolite EXP3179 for PPARgamma activation. Hypertension (Dallas, Tex. : 1979). 2009 Oct; 54(4):738-43. doi: 10.1161/hypertensionaha.109.132886. [PMID: 19687349]
  • Hiten J Shah, Mohan L Kundlik, Nitesh K Patel, Gunta Subbaiah, Dasharath M Patel, Bhanubhai N Suhagia, Chhagan N Patel. Rapid determination of losartan and losartan acid in human plasma by multiplexed LC-MS/MS. Journal of separation science. 2009 Oct; 32(20):3388-94. doi: 10.1002/jssc.200900287. [PMID: 19750501]
  • Z Li, G Wang, L-S Wang, W Zhang, Z-R Tan, L Fan, B-L Chen, Q Li, J Liu, J-H Tu, D-L Hu, Z-Q Liu, H-H Zhou. Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy male subjects. Xenobiotica; the fate of foreign compounds in biological systems. 2009 Oct; 39(10):788-93. doi: 10.1080/00498250903134435. [PMID: 19604036]
  • Guo Wang, Chang-Qiong Xiao, Zhi Li, Dong Guo, Yao Chen, Lan Fan, Rong-Hua Qian, Xiu-Juan Peng, Dong-Li Hu, Hong-Hao Zhou. Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers. The Annals of pharmacotherapy. 2009 Jun; 43(6):1045-9. doi: 10.1345/aph.1l690. [PMID: 19458107]
  • Arzu Gunes, Erhan Bilir, Hakan Zengil, Melih O Babaoglu, Atila Bozkurt, Umit Yasar. Inhibitory effect of valproic acid on cytochrome P450 2C9 activity in epilepsy patients. Basic & clinical pharmacology & toxicology. 2007 Jun; 100(6):383-6. doi: 10.1111/j.1742-7843.2007.00061.x. [PMID: 17516991]
  • Filomila Kolocouri, Yannis Dotsikas, Constantinos Apostolou, Constantinos Kousoulos, Yannis L Loukas. Simultaneous determination of losartan, EXP-3174 and hydrochlorothiazide in plasma via fully automated 96-well-format-based solid-phase extraction and liquid chromatography-negative electrospray tandem mass spectrometry. Analytical and bioanalytical chemistry. 2007 Jan; 387(2):593-601. doi: 10.1007/s00216-006-0990-4. [PMID: 17119933]
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  • Tiziano Tuccinardi, Vincenzo Calderone, Simona Rapposelli, Adriano Martinelli. Proposal of a new binding orientation for non-peptide AT1 antagonists: homology modeling, docking and three-dimensional quantitative structure-activity relationship analysis. Journal of medicinal chemistry. 2006 Jul; 49(14):4305-16. doi: 10.1021/jm060338p. [PMID: 16821790]
  • Jean-Francois Marier, Rudolf Guilbaud, Siva Rama Prasad Kambhampati, Philip Mathew, James Moberly, James Lee, Daniel E Salazar. The effect of AST-120 on the single-dose pharmacokinetics of losartan and losartan acid (E-3174) in healthy subjects. Journal of clinical pharmacology. 2006 Mar; 46(3):310-20. doi: 10.1177/0091270005284388. [PMID: 16490807]
  • Arzu Gunes, Ugur Coskun, Cem Boruban, Nazan Gunel, Melih O Babaoglu, Orhan Sencan, Atila Bozkurt, Anders Rane, Moustapha Hassan, Hakan Zengil, Umit Yasar. Inhibitory effect of 5-fluorouracil on cytochrome P450 2C9 activity in cancer patients. Basic & clinical pharmacology & toxicology. 2006 Feb; 98(2):197-200. doi: 10.1111/j.1742-7843.2006.pto_304.x. [PMID: 16445595]
  • Wilko Spiering, Abraham A Kroon, Monique Jmj Fuss-Lejeune, Peter W de Leeuw. Genetic contribution to the acute effects of angiotensin II type 1 receptor blockade. Journal of hypertension. 2005 Apr; 23(4):753-8. doi: 10.1097/01.hjh.0000163143.66965.06. [PMID: 15775779]
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