In Vitro Analysis of AKR1D1 Interactions with Clopidogrel: Effects on Enzyme Activity and Gene Expression
References
- Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267–315.
- Geisler T, Schaeffeler E, Dippon J, Winter S, Buse V, Bischofs C, et al. CYP2C19 and nongenetic factors predict poor responsiveness to clopidogrel loading dose after coronary stent implantation. Pharmacog-enomics. 2008 Sep;9(9):1251–9.
- Qu J, Zhang H, Rao C, Chen S, Zhao Y, Sun H, et al. Dual Antiplatelet Therapy with Clopidogrel and Aspirin Versus Aspirin Monotherapy in Patients Undergoing Coronary Artery Bypass Graft Surgery. J Am Heart Assoc. 2021 Jun;10(11):e020413.
- Tan BEX, Wong PY, Baibhav B, Thakkar S, Azhar AZ, Rao M, et al. Clopidogrel Vs Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis. Current Problems in Cardiology. 2023 Aug 1;48(8):101174.
- Gurbel PA, Tantry US. Clopidogrel resistance? Thromb Res. 2007;120(3):311–21.
- Hawken TN, Berenson AM, Klopfenstein J, Leithead CC, Brinster CJ, Sternbergh WC, et al. Clopidogrel Resistance Is Common in Patients Undergoing Vascular and Coronary Interventions. Journal of Vascular Surgery. 2021 Jan 1;73(1):e25–6.
- Ma TKW, Lam YY, Tan VP, Yan BP. Variability in response to clopidogrel: how important are pharmacogenetics and drug interactions? British Journal of Clinical Pharmacology. 2011 Oct;72(4):697.
- Ray S. Clopidogrel resistance: The way forward. Indian Heart Journal. 2014 Sep;66(5):530.
- Giantini A, Timan IS, Dharma R, Sukmawan R, Setiabudy R, Alwi I, et al. The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention. Frontiers in Cardiovascular Medicine. 2023 Feb 8;9:1027892.
- Sangkuhl K, Klein TE, Altman RB. Clopidogrel pathway. Pharmacogenetics and Genomics. 2010 Jul;20(7):463.
- Savi P, Herbert JM, Pflieger AM, Dol F, Delebassee D, Combalbert J, et al. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochemical Pharmacology. 1992 Aug 4;44(3):527–32.
- Jiang XL, Samant S, Lesko LJ, Schmidt S. Clinical pharmacokinetics and pharmacodynamics of clopi-dogrel. Clin Pharmacokinet. 2015 Feb;54(2):147–66.
- Pan Y, Chen W, Xu Y, Yi X, Han Y, Yang Q, et al. Genetic Polymorphisms and Clopidogrel Efficacy for Acute Ischemic Stroke or Transient Ischemic Attack. Circulation. 2017 Jan 3;135(1):21–33.
- Hou X, Shi J, Sun H. Gene polymorphism of cytochrome P450 2C19*2 and clopidogrel resistance reflected by platelet function assays: a meta-analysis. Eur J Clin Pharmacol. 2014 Sep;70(9):1041–7.
- Ford NF. The Metabolism of Clopidogrel: CY-P2C19 Is a Minor Pathway. J Clin Pharmacol. 2016 Dec;56(12):1474–83.
- Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics. 2013 Apr 1;138(1):103–41.
- Barski OA, Tipparaju SM, Bhatnagar A. The aldoketo reductase superfamily and its role in drug metabolism and detoxification. Drug Metab Rev. 2008;40(4):553–624.
- Nikolaou N, Gathercole LL, Kirkwood L, Dunford JE, Hughes BA, Gilligan LC, et al. AKR1D1 regulates glucocorticoid availability and glucocorticoid receptor activation in human hepatoma cells. The Journal of Steroid Biochemistry and Molecular Biology. 2019 May 1;189:218–27.
- Penning TM, Wangtrakuldee P, Auchus RJ. Structural and Functional Biology of Aldo-Keto Reductase Steroid-Transforming Enzymes. Endocr Rev. 2019 Apr 1;40(2):447–75.
- Chen M, Penning TM. 5β-Reduced steroids and human Δ(4)-3-ketosteroid 5β-reductase (AKR1D1). Steroids. 2014 May;83:17–26.
- Chaudhry AS, Thirumaran RK, Yasuda K, Yang X, Fan Y, Strom SC, et al. Genetic Variation in AldoKeto Reductase 1D1 (<em>AKR1D1</em>) Affects the Expression and Activity of Multiple Cytochrome P450s. Drug Metab Dispos. 2013 Aug;41(8):1538–47.
- Kapedanovska-Nestorovska A, Dimovski AJ, Sterjev Z, Matevska Geskovska N, Suturkova L, Ugurov P, et al. The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome. Pharmgenomics Pers Med. 2019 Oct; 12:287–95.
- Green MR, Sambrook J. Molecular Cloning: A Laboratory Manual. 4th ed. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2012.
- Brown TA. Gene Cloning and DNA Analysis: An Introduction. 8th ed. Hoboken (NJ): Wiley-Blackwell; 2020.
- Shutevska K, Nestorovska AK. Cloning, expression, and purification of recombinant AKR1D1 for therapeutic applications. Acta Pharm. 2024 Dec 17; doi: <a href="https://doi.org/10.2478/acph-2025-0003." target="_blank" rel="noopener noreferrer" class="text-signal-blue hover:underline">10.2478/acph-2025-0003.</a> Online ahead of print.
- Möller G, Temml V, Cala Peralta A, Gruet O, Rich-omme P, Séraphin D, et al. Analogues of Natural Chalcones as Efficient Inhibitors of AKR1C3. Metabolites. 2022 Feb;12(2):99.
- Nikolaou N, Gathercole LL, Marchand L, Althari S, Dempster NJ, Green CJ, et al. AKR1D1 is a novel regulator of metabolic phenotype in human hepatocytes and is dysregulated in non-alcoholic fatty liver disease. Metabolism. 2019 Oct;99:67–80.
- Kędzierski J, Allard JA, Odermatt A, Smieško M. Assessment of the inhibitory potential of anabolic steroids towards human AKR1D1 by computational methods and <em>in vitro</em> evaluation. Toxicology Letters. 2023 Aug 1;384:1–13.
- Laurence L. Brunton, Randa Hilal-Dandan, Bjorn Knollmann, editors. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. New York, NY, USA: McGraw Hill Education, 2017.
- Rižner TL, Penning TM. Role of Aldo-Keto Reductase Family 1 (AKR1) Enzymes in Human Steroid Metabolism. Steroids. 2013 Nov 1;79:<a href="https://doi.org/10.1016/j.ster-oids.2013.10.012." target="_blank" rel="noopener noreferrer" class="text-signal-blue hover:underline">10.1016/j.ster-oids.2013.10.012.</a>
- Chen M, Drury JE, Penning TM. Substrate specificity and inhibitor analyses of human steroid 5β-reductase (AKR1D1). Steroids. 2011 Apr;76(5):484–90.
- Chen M, Drury JE, Christianson DW, Penning TM. Conversion of Human Steroid 5β-Reductase (AKR1D1) into 3β-Hydroxysteroid Dehydrogenase by Single Point Mutation E120H. Journal of Biological Chemistry. 2012 May 11;287(20):16609–22.
DOI: https://doi.org/10.2478/bjmg-2024-0012 | Journal eISSN: 2199-5761
Language: English
Page range: 69 - 75
Published on: Mar 6, 2025
Published by: Macedonian Academy of Sciences and Arts
In partnership with: Paradigm Publishing Services
Publication frequency: 2 times per year
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© 2025 K Shutevska, Panovska T Kadifkova, Z Zhivikj, Nestorovska A Kapedanovska, published by Macedonian Academy of Sciences and Arts
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.