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image of Bempedoic Acid's Chemistry, Pharmacological Characteristics and Bioanalytical Techniques: An Updated Review

Abstract

Background

Elevated blood cholesterol has been established as a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Adults with hyperlipidemia have a significantly increased risk of developing cardiovascular diseases (CVD). First-line treatments for hyperlipidemia include statins, which help raise HDL-C levels in cases of severe and familial hypercholesterolemia and decrease LDL-C and TG levels. Numerous adverse effects on muscles have been associated with statins, such as asymptomatic elevations in blood creatine kinase activity and potentially fatal rhabdomyolysis. Non-statin drugs are advised for people whose very high cardiovascular risk or heterozygous familial hypercholesterolemia make statin therapy insufficient. A novel lipid-lowering medication with a distinct mode of action is bempedoic acid.

Elevated blood cholesterol is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Individuals with hyperlipidemia are at a higher risk for developing cardiovascular diseases. Statins are the primary treatment for hyperlipidemia, raising HDL-C levels and lowering LDL-C and TG levels. However, statins can adversely affect muscles, including muscle-related complications like increased blood creatine kinase activity and rhabdomyolysis. Therefore, non-statin drugs may be recommended for individuals. Bempedoic acid is a brand-new, first-in-class, oral small molecule that inhibits cholesterol manufacturing like statins, consequently reducing low-density lipoprotein cholesterol (LDL-C) through activating LDL receptors.

Methods

This study offers helpful information on how to utilize bempedoic acid to decrease LDL-C, as well as recommendations for which individuals could benefit and safety monitoring tips during therapy. A novel family of drugs called bempedoic acid is identified as a prodrug that becomes bempedoyl-CoA in the liver an enzyme called very longchain consisting of acyl-CoA synthetase 1. Bempedoic acid can control cholesterol metabolism. Low-density lipoprotein cholesterol levels appeared to be dramatically reduced by bempedoic acid, according to clinical investigations. The toleration of bempedoic acid was good.

Results

A cardiovascular outcomes trial is now evaluating bempedoic acid to determine its impact on major cardiovascular events in patients with or at high risk for cardiovascular disease and statin intolerance.

Conclusion

This review describes the chemistry, mechanism of action, pharmacokinetics, analytical potential, and safety of bempedoic acid. Bempedoic acid is an effective and often well-tolerated drug used to further reduce LDL-C levels in patients taking the maximum dosage of tolerated statins or to control LDL-C levels in persons who can not take statins. The results of the clear Outcomes research, which is looking into whether bempedoic acid might reduce the frequency of serious cardiovascular events, are expected in 2025.

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2024-11-22
2025-01-19

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References

  1. Mihaylova B. Emberson J. Blackwell L. Keech A. Simes J. Barnes E.H. Voysey M. Gray A. Collins R. Baigent C. Cholesterol Treatment Trialists’ (CTT) Collaborators The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet 2012 380 9841 581 590 10.1016/S0140‑6736(12)60367‑5 22607822
    [Google Scholar]
  2. Agarwala A. Goldberg A.C. Bempedoic acid: A promising novel agent for LDL-C lowering. Future Cardiol. 2020 16 5 361 371 10.2217/fca‑2020‑0016 32463301
    [Google Scholar]
  3. Arnett D.K. Blumenthal R.S. Albert M.A. Buroker A.B. Goldberger Z.D. Hahn E.J. Himmelfarb C.D. Khera A. Lloyd-Jones D. McEvoy J.W. Michos E.D. Miedema M.D. Muñoz D. Smith S.C. Jr Virani S.S. Williams K.A. Sr Yeboah J. Ziaeian B. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: A report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation 2019 140 11 10.1161/CIR.0000000000000678
    [Google Scholar]
  4. Grundy S.M. Stone N.J. Bailey A.L. Beam C. Birtcher K.K. Birtcher R.S. Braun L.T. Ferranti S. Faiella-Tommasino J. Forman D.E. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: Executive summary: A report of the American college of Cardiology/American heart association task force on clinical practice guidelines. Circulation 2019 139 25
    [Google Scholar]
  5. Cannon C.P. Blazing M.A. Giugliano R.P. McCagg A. White J.A. Theroux P. Darius H. Lewis B.S. Ophuis T.O. Jukema J.W. De Ferrari G.M. Ruzyllo W. De Lucca P. Im K. Bohula E.A. Reist C. Wiviott S.D. Tershakovec A.M. Musliner T.A. Braunwald E. Califf R.M. IMPROVE-IT Investigators Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 2015 372 25 2387 2397 10.1056/NEJMoa1410489 26039521
    [Google Scholar]
  6. Bonovas S. Nikolopoulos G. Sitaras N.M. Efficacy and safety of more intensive lowering of LDL cholesterol. Lancet 2011 377 9767 715 10.1016/S0140‑6736(11)60261‑4 21353894
    [Google Scholar]
  7. Silverman M.G. Ference B.A. Im K. Wiviott S.D. Giugliano R.P. Grundy S.M. Braunwald E. Sabatine M.S. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions. JAMA 2016 316 12 1289 1297 10.1001/jama.2016.13985 27673306
    [Google Scholar]
  8. Jean-Louis Henri DasseuxDaniela Carmen Oniciu Hydroxyl compounds and compositions for cholesterol management and related uses. Patent WO2004067489A2 2003
  9. Paton D.M. Paton, D.M. Bempedoic acid. ATP-citrate lyase inhibitor, AMPK activator, Treatment of hypercholesterolemia. Drugs Future 2017 42 4 0201 10.1358/dof.2017.042.04.2530248
    [Google Scholar]
  10. Gundamalla R. Bantu R. Reddy B.V.S. TosMIC-free synthesis of bempedoic acid, a hypercholesterolemia drug. ARKIVOC 2024 2024 7 10.24820/ark.5550190.p012.204
    [Google Scholar]
  11. Yang J. Bempedoic acid for the treatment of hypercholesterolemia. Expert Rev. Cardiovasc. Ther. 2020 18 7 373 380 10.1080/14779072.2020.1782744 32532162
    [Google Scholar]
  12. U.S. Food and Drug Administration.NEXLETOL(Bempedoic Acid) tablet for oral use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/211616s012s013lbl.pdf 2020
  13. Pinkosky S.L. Filippov S. Srivastava R.A.K. Hanselman J.C. Bradshaw C.D. Hurley T.R. Cramer C.T. Spahr M.A. Brant A.F. Houghton J.L. Baker C. Naples M. Adeli K. Newton R.S. AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism. J. Lipid Res. 2013 54 1 134 151 10.1194/jlr.M030528 23118444
    [Google Scholar]
  14. Lemus H.N. Mendivil C.O. Adenosine triphosphate citrate lyase: Emerging target in the treatment of dyslipidemia. J. Clin. Lipidol. 2015 9 3 384 389 10.1016/j.jacl.2015.01.002 26073398
    [Google Scholar]
  15. Barter P.J. Rye K.A. New Era of Lipid-Lowering Drugs. Pharmacol. Rev. 2016 68 2 458 475 10.1124/pr.115.012203 26983688
    [Google Scholar]
  16. Turner T. Stein E.A. Non-statin treatments for managing LDL cholesterol and their outcomes. Clin. Ther. 2015 37 12 2751 2769 10.1016/j.clinthera.2015.09.004 26548322
    [Google Scholar]
  17. Bove M. Cicero A.F.G. Borghi C. Emerging drugs for the treatment of hypercholesterolemia. Expert Opin. Emerg. Drugs 2019 24 1 63 69 10.1080/14728214.2019.1591372 30841759
    [Google Scholar]
  18. Nikolic D. Mikhailidis D.P. Davidson M.H. Rizzo M. Banach M. ETC-1002: A future option for lipid disorders? Atherosclerosis 2014 237 2 705 710 10.1016/j.atherosclerosis.2014.10.099 25463109
    [Google Scholar]
  19. Aljuffali I.A. Sung C.T. Shen F.M. Huang C.T. Fang J.Y. Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells. AAPS J. 2014 16 1 140 150 10.1208/s12248‑013‑9550‑y 24307611
    [Google Scholar]
  20. Pinkosky S.L. Newton R.S. Day E.A. Ford R.J. Lhotak S. Austin R.C. Birch C.M. Smith B.K. Filippov S. Groot P.H.E. Steinberg G.R. Lalwani N.D. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat. Commun. 2016 7 1 13457 10.1038/ncomms13457 27892461
    [Google Scholar]
  21. Bazilevsky G.A. Affronti H.C. Wei X. Campbell S.L. Wellen K.E. Marmorstein R. ATP-citrate lyase multimerization is required for coenzyme-A substrate binding and catalysis. J. Biol. Chem. 2019 294 18 7259 7268 10.1074/jbc.RA118.006685 30877197
    [Google Scholar]
  22. Burke A.C. Telford D.E. Huff M.W. Bempedoic acid: Effects on lipoprotein metabolism and atherosclerosis. Curr. Opin. Lipidol. 2019 30 1 1 9 10.1097/MOL.0000000000000565 30586346
    [Google Scholar]
  23. Cicero A.F.G. Fogacci F. Hernandez A.V. Banach M. Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP) Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis. PLoS Med. 2020 17 7 e1003121 10.1371/journal.pmed.1003121 32673317
    [Google Scholar]
  24. Edwards G.B. Muthurajan U.M. Bowerman S. Luger K. Analytical Ultracentrifugation (AUC): An overview of the application of fluorescence and absorbance AUC to the study of biological macromolecules. Curr. Protoc. Mol. Biol. 2020 133 1 e131 10.1002/cpmb.131 33351266
    [Google Scholar]
  25. Gunn L.H. McKay A.J. Feng A. Louie M.J. Ballantyne C.M. Ray K.K. Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease. Atherosclerosis Plus 2022 49 20 27 10.1016/j.athplu.2022.05.003 36644205
    [Google Scholar]
  26. Markham A. Bempedoic acid: First approval. Drugs 2020 80 7 747 753 10.1007/s40265‑020‑01308‑w 32314225
    [Google Scholar]
  27. Lalwani N.D. Hanselman J.C. MacDougall D.E. Sterling L.R. Cramer C.T. Complementary low-density lipoprotein-cholesterol lowering and pharmacokinetics of adding bempedoic acid (ETC-1002) to high-dose atorvastatin background therapy in hypercholesterolemic patients: A randomized placebo-controlled trial. J. Clin. Lipidol. 2019 13 4 568 579 10.1016/j.jacl.2019.05.003 31202641
    [Google Scholar]
  28. Biolo G. Vinci P. Mangogna A. Landolfo M. Schincariol P. Fiotti N. Mearelli F. Di Girolamo F.G. Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome. Front. Cardiovasc. Med. 2022 9 1028355 10.3389/fcvm.2022.1028355 36386319
    [Google Scholar]
  29. Tummala R. Gupta M. Devanabanda A.R. Bandyopadhyay D. Aronow W.S. Ray K.K. Mamas M. Ghosh R.K. Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis. Ann. Med. 2022 54 1 1287 1296 10.1080/07853890.2022.2059559 35533049
    [Google Scholar]
  30. Ruscica M. Sirtori C.R. Carugo S. Banach M. Corsini A. Bempedoic Acid: For Whom and When. Curr. Atheroscler. Rep. 2022 24 10 791 801 10.1007/s11883‑022‑01054‑2 35900636
    [Google Scholar]
  31. Rimbach G. Park Y.C. Guo Q. Moini H. Qureshi N. Saliou C. Takayama K. Virgili F. Packer L. Nitric oxide synthesis and TNF-α secretion in RAW 264.7 macrophages. Life Sci. 2000 67 6 679 694 10.1016/S0024‑3205(00)00664‑0 12659174
    [Google Scholar]
  32. Sharma S. Goyal S. Chauhan K. A review on analytical method development and validation. Int. J. Appl. Pharm. 2018 10 6 8 10.22159/ijap.2018v10i6.28279
    [Google Scholar]
  33. Gałuszka A. Migaszewski Z. Namieśnik J. The 12 principles of green analytical chemistry and the significance mnemonic of green analytical practices. Trends Analyt. Chem. 2013 50 78 84 10.1016/j.trac.2013.04.010
    [Google Scholar]
  34. Moore P.H. Phenotypic and genetic diversity of papaya. Genetics and Genomics of Papaya. Springer 2014 35 45 10.1007/978‑1‑4614‑8087‑7_3
    [Google Scholar]
  35. Paul S. Barai L. Husen F. Sarker S. Pal T.K. Bai P. Matin Sarker M.A. Saima Alam S. Biswas S. Analytical method development and validation for estimation of ranitidine in solid dosage form by UV-spectrophotometric method. Orient. J. Chem. 2020 36 6 1161 1167 10.13005/ojc/360621
    [Google Scholar]
  36. Quijia C.R. Chorilli M. Characteristics, biological properties and analytical methods of Piperine: A review. Crit. Rev. Anal. Chem. 2020 50 1 62 77 10.1080/10408347.2019.1573656 30810335
    [Google Scholar]
  37. Nisha S. Kumar A.S. Electrochemical conversion of triamterene-diuretic drug to hydroxybenzene-triamterene intermediate mimicking the pharmacokinetic reaction on multiwalled carbon nanotube surface and its electrocatalytic oxidation function of thiol. J. Electroanal. Chem. (Lausanne) 2019 839 214 223 10.1016/j.jelechem.2019.03.039
    [Google Scholar]
  38. Lautre C. Sharma S. Sahu J.K. Chemistry, biological properties and analytical methods of Levonadifloxacin: A review. Crit. Rev. Anal. Chem. 2022 52 5 1069 1077 10.1080/10408347.2020.1855412 33307757
    [Google Scholar]
  39. Molleti D. Amgoth K.P. Pallekona S. Stability indicating method development and validation for the estimation of Bempedoic acid and ezetimibe by reverse Phase– ultra performance liquid chromatography. Int. J. Pharm. Sci. Drug Res. 2021 13 05 559 564 10.25004/IJPSDR.2021.130514
    [Google Scholar]
  40. Yarra U.S.T. Gummadi S. Stability indicating RP-UPLC method for simultaneous quantification of bempedoic acid and ezetimibe in bulk and pharmaceutical formulations. future j. pharm. sci. 2021 7 1 209 10.1186/s43094‑021‑00363‑8
    [Google Scholar]
  41. Engel B.J. Preusch K. Brown C. Cramer C.T. Shoup R. Measurement of bempedoic acid and its keto metabolite in human plasma and urine using solid phase extraction and electrospray LC-MS/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2020 1154 122291 10.1016/j.jchromb.2020.122291 32763847
    [Google Scholar]
  42. Karla V.R. Raghasudha M. Chitta R. Simultaneous determination of bempedoic acid and Ezetimibe in rat plasma using HPLC–PDA and its applications to a pharmacokinetic study. Chem. Africa 2022 5 4 917 927 10.1007/s42250‑022‑00392‑7
    [Google Scholar]
  43. Vejendla A. Talari S. Ramu G. Rajani C. Characterization of novel stress degradation products of Bempedoic acid and Ezetimibe using UPLC – MS / MS: Development and validation of stability - indicating UPLC method Futur. J. Pharm. Sci. 2021 234 10.1186/s43094‑021‑00381‑6
    [Google Scholar]
  44. Gaikwad J. Sharma S. Hatware K.V. Review on characteristics and analytical methods of Tazarotene: An update. Crit. Rev. Anal. Chem. 2020 50 1 90 96 10.1080/10408347.2019.1586519 30942085
    [Google Scholar]
  45. Poliakoff M. Licence P. Green chemistry. Nature 2007 450 7171 810 812 10.1038/450810a 18064000
    [Google Scholar]
  46. Prat D. Hayler J. Wells A. A survey of solvent selection guides. Green Chem. 2014 16 10 4546 4551 10.1039/C4GC01149J
    [Google Scholar]
  47. Anastas P.T. Green chemistry and the role of analytical methodology development. Crit. Rev. Anal. Chem. 1999 29 3 167 175 10.1080/10408349891199356
    [Google Scholar]
  48. Zuin V.G. Eilks I. Elschami M. Kümmerer K. Education in green chemistry and in sustainable chemistry: Perspectives towards sustainability. Green Chem. 2021 23 4 1594 1608 10.1039/D0GC03313H
    [Google Scholar]
  49. Tan H. Li J. He M. Li J. Zhi D. Qin F. Zhang C. Global evolution of research on green energy and environmental technologies:A bibliometric study. J. Environ. Manage. 2021 297 113382 10.1016/j.jenvman.2021.113382 34332345
    [Google Scholar]
  50. Zimmerman J. B. Anastas P. T. Erythropel H. C. Leitner W. Designing for a green chemistry future Science 6476 2020 367 396 400 10.1126/science.aay3060
    [Google Scholar]
  51. Shirkhedkar A.A. Chaudhari S.R. Exploring an experimental combination of analytical quality by design and green analytical chemistry approaches for development of HPTLC densitometric protocol for the analysis of barnidipine hydrochloride. Biomed. Chromatogr. 2022 36 1 e5244 10.1002/bmc.5244 34528268
    [Google Scholar]
  52. García-Quintero A. Palencia M. A critical analysis of environmental sustainability metrics applied to green synthesis of nanomaterials and the assessment of environmental risks associated with the nanotechnology. Sci. Total Environ. 2021 793 148524 10.1016/j.scitotenv.2021.148524 34182452
    [Google Scholar]
  53. Zidny R. Eilks I. Learning about pesticide use adapted from ethnoscience as a contribution to green and sustainable chemistry education. Educ. Sci. 2022 12 4 227 10.3390/educsci12040227
    [Google Scholar]
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Bempedoic Acid's Chemistry, Pharmacological Characteristics and Bioanalytical Techniques: An Updated Review
Bentham Science Publishers ; https://doi.org/10.2174/0115734110335673241119051406
/content/journals/cac/10.2174/0115734110335673241119051406
/content/journals/cac/10.2174/0115734110335673241119051406
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  • Article Type:     Review Article
Keywords: bioanalytical ; hyperlipidemia ; Cardiovascular disease ; hypercholesterolemia ; bempedoic acid ; low-density lipoprotein cholesterol

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