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AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin.

Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, Rappley I, Vogel H, Liedtke M, Witteles RM, Powers ET, Reixach N, Chan WK, Wilson IA, Kelly JW, Graef IA, Alhamadsheh MM
Proc Natl Acad Sci U S A 110 9992-7 (2013)
Cited: 83 times
EuropePMC logo PMID: 23716704

Abstract

The misassembly of soluble proteins into toxic aggregates, including amyloid fibrils, underlies a large number of human degenerative diseases. Cardiac amyloidoses, which are most commonly caused by aggregation of Ig light chains or transthyretin (TTR) in the cardiac interstitium and conducting system, represent an important and often underdiagnosed cause of heart failure. Two types of TTR-associated amyloid cardiomyopathies are clinically important. The Val122Ile (V122I) mutation, which alters the kinetic stability of TTR and affects 3% to 4% of African American subjects, can lead to development of familial amyloid cardiomyopathy. In addition, aggregation of WT TTR in individuals older than age 65 y causes senile systemic amyloidosis. TTR-mediated amyloid cardiomyopathies are chronic and progressive conditions that lead to arrhythmias, biventricular heart failure, and death. As no Food and Drug Administration-approved drugs are currently available for treatment of these diseases, the development of therapeutic agents that prevent TTR-mediated cardiotoxicity is desired. Here, we report the development of AG10, a potent and selective kinetic stabilizer of TTR. AG10 prevents dissociation of V122I-TTR in serum samples obtained from patients with familial amyloid cardiomyopathy. In contrast to other TTR stabilizers currently in clinical trials, AG10 stabilizes V122I- and WT-TTR equally well and also exceeds their efficacy to stabilize WT and mutant TTR in whole serum. Crystallographic studies of AG10 bound to V122I-TTR give valuable insights into how AG10 achieves such effective kinetic stabilization of TTR, which will also aid in designing better TTR stabilizers. The oral bioavailability of AG10, combined with additional desirable drug-like features, makes it a very promising candidate to treat TTR amyloid cardiomyopathy.

Reviews - 4his mentioned but not cited (1)

  1. How Structural Biologists and the Protein Data Bank Contributed to Recent FDA New Drug Approvals. Westbrook JD, Burley SK. Structure 27 211-217 (2019)

Articles - 4his mentioned but not cited (5)

  1. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, Rappley I, Vogel H, Liedtke M, Witteles RM, Powers ET, Reixach N, Chan WK, Wilson IA, Kelly JW, Graef IA, Alhamadsheh MM. Proc Natl Acad Sci U S A 110 9992-9997 (2013)
  2. Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity. Sant'Anna R, Gallego P, Robinson LZ, Pereira-Henriques A, Ferreira N, Pinheiro F, Esperante S, Pallares I, Huertas O, Almeida MR, Reixach N, Insa R, Velazquez-Campoy A, Reverter D, Reig N, Ventura S. Nat Commun 7 10787 (2016)
  3. Overcoming universal restrictions on metal selectivity by protein design. Choi TS, Tezcan FA. Nature 603 522-527 (2022)
  4. Molecular dynamics simulation study of AG10 and tafamidis binding to the Val122Ile transthyretin variant. Morris KF, Geoghegan RM, Palmer EE, George M, Fang Y. Biochem Biophys Rep 21 100721 (2020)
  5. Molecular Determinants of Filament Capping Proteins Required for the Formation of Functional Flagella in Gram-Negative Bacteria. Nedeljković M, Postel S, Pierce BG, Sundberg EJ. Biomolecules 11 1397 (2021)


Reviews citing this publication (39)

  1. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. J Am Coll Cardiol 73 2872-2891 (2019)
  2. Chemically induced proximity in biology and medicine. Stanton BZ, Chory EJ, Crabtree GR, Crabtree GR. Science 359 eaao5902 (2018)
  3. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Castaño A, Drachman BM, Judge D, Maurer MS. Heart Fail Rev 20 163-178 (2015)
  4. Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis. Coelho T, Merlini G, Bulawa CE, Fleming JA, Judge DP, Kelly JW, Maurer MS, Planté-Bordeneuve V, Labaudinière R, Mundayat R, Riley S, Lombardo I, Huertas P. Neurol Ther 5 1-25 (2016)
  5. Transthyretin familial amyloid polyneuropathy: an update. Plante-Bordeneuve V. J Neurol 265 976-983 (2018)
  6. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. Yamamoto H, Yokochi T. ESC Heart Fail 6 1128-1139 (2019)
  7. Alternative modulation of protein-protein interactions by small molecules. Fischer G, Rossmann M, Hyvönen M. Curr Opin Biotechnol 35 78-85 (2015)
  8. Advances in the treatment of hereditary transthyretin amyloidosis: A review. Gertz MA, Mauermann ML, Grogan M, Coelho T. Brain Behav 9 e01371 (2019)
  9. Inflammatory and Molecular Pathways in Heart Failure-Ischemia, HFpEF and Transthyretin Cardiac Amyloidosis. Michels da Silva D, Langer H, Graf T. Int J Mol Sci 20 E2322 (2019)
  10. An overview of drugs currently under investigation for the treatment of transthyretin-related hereditary amyloidosis. Obici L, Merlini G. Expert Opin Investig Drugs 23 1239-1251 (2014)
  11. Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis. Mathew V, Wang AK. Drug Des Devel Ther 13 1515-1525 (2019)
  12. Pathophysiology and Therapeutic Approaches to Cardiac Amyloidosis. Griffin JM, Rosenblum H, Maurer MS. Circ Res 128 1554-1575 (2021)
  13. ATTR Amyloidosis: Current and Emerging Management Strategies: JACC: CardioOncology State-of-the-Art Review. Griffin JM, Rosenthal JL, Grodin JL, Maurer MS, Grogan M, Cheng RK. JACC CardioOncol 3 488-505 (2021)
  14. Transthyretin Cardiac Amyloidosis in Older Americans. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. J Card Fail 22 996-1003 (2016)
  15. Transthyretin cardiac amyloidosis: pathogenesis, treatments, and emerging role in heart failure with preserved ejection fraction. Ton VK, Mukherjee M, Judge DP. Clin Med Insights Cardiol 8 39-44 (2014)
  16. Tafamidis: a review of its use in familial amyloid polyneuropathy. Scott LJ. Drugs 74 1371-1378 (2014)
  17. Advances in the Treatment of Cardiac Amyloidosis. Macedo AVS, Schwartzmann PV, de Gusmão BM, Melo MDT, Coelho-Filho OR. Curr Treat Options Oncol 21 36 (2020)
  18. Current and future treatment of amyloid neuropathies. Adams D, Cauquil C, Theaudin M, Rousseau A, Algalarrondo V, Slama MS. Expert Rev Neurother 14 1437-1451 (2014)
  19. Amyloidosis-the Diagnosis and Treatment of an Underdiagnosed Disease. Ihne S, Morbach C, Sommer C, Geier A, Knop S, Störk S. Dtsch Arztebl Int 117 159-166 (2020)
  20. Emerging Therapeutics for the Treatment of Light Chain and Transthyretin Amyloidosis. Zhang KW, Stockerl-Goldstein KE, Lenihan DJ. JACC Basic Transl Sci 4 438-448 (2019)
  21. Novel pharmacotherapies for cardiac amyloidosis. Alexander KM, Singh A, Falk RH. Pharmacol Ther 180 129-138 (2017)
  22. Molecular Mechanisms of Cardiac Amyloidosis. Saito Y, Nakamura K, Ito H. Int J Mol Sci 23 25 (2021)
  23. Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses. Nevone A, Merlini G, Nuvolone M. Front Pharmacol 11 1024 (2020)
  24. Emerging therapeutic targets currently under investigation for the treatment of systemic amyloidosis. Nuvolone M, Merlini G. Expert Opin Ther Targets 21 1095-1110 (2017)
  25. Modulation of the Mechanisms Driving Transthyretin Amyloidosis. Bezerra F, Saraiva MJ, Almeida MR. Front Mol Neurosci 13 592644 (2020)
  26. Diagnosis and treatment of heart failure in hereditary transthyretin amyloidosis. Puig-Carrion GD, Reyentovich A, Katz SD. Clin Auton Res 29 45-53 (2019)
  27. Advances in Treatment of Cardiac Amyloid. Dahm CN, Cornell RF, Lenihan DJ. Curr Treat Options Cardiovasc Med 20 37 (2018)
  28. Diagnosis and treatment of transthyretin-related amyloidosis cardiomyopathy. Teng C, Li P, Bae JY, Pan S, Dixon RAF, Liu Q. Clin Cardiol 43 1223-1231 (2020)
  29. Current and Emerging Therapies for Hereditary Transthyretin Amyloidosis: Strides Towards a Brighter Future. Obici L, Mussinelli R. Neurotherapeutics 18 2286-2302 (2021)
  30. Disease-modifying therapy for proteinopathies: Can the exception become the rule? Bitan G. Prog Mol Biol Transl Sci 168 277-287 (2019)
  31. Emerging Therapies for Transthyretin Cardiac Amyloidosis. Alexander KM, Evangelisti A, Witteles RM. Curr Treat Options Cardiovasc Med 21 40 (2019)
  32. Changing paradigm in the treatment of amyloidosis: From disease-modifying drugs to anti-fibril therapy. Quarta CC, Fontana M, Damy T, Catini J, Simoneau D, Mercuri M, Garcia-Pavia P, Maurer MS, Palladini G. Front Cardiovasc Med 9 1073503 (2022)
  33. Cardiac Transthyretin-derived Amyloidosis: An Emerging Target in Heart Failure with Preserved Ejection Fraction? Klaassen SH, van Veldhuisen DJ, Nienhuis H, van den Berg MP, Hazenberg BP, van der Meer P. Card Fail Rev 6 e21 (2020)
  34. Targeted treatments of AL and ATTR amyloidosis. Chandrashekar P, Desai AK, Trachtenberg BH. Heart Fail Rev 27 1587-1603 (2022)
  35. The quintessential form of diastolic heart failure in older adults: Wild type transthyretin cardiac amyloidosis. Driggin E, Maurer MS. Clin Cardiol 43 171-178 (2020)
  36. Cardiac amyloidosis: evolving pathogenesis, multimodal diagnostics, and principles of treatment. Medarametla GD, Kahlon RS, Mahitha L, Shariff S, Vakkalagadda NP, Chopra H, Kamal MA, Patel N, Sethi Y, Kaka N. EXCLI J 22 781-808 (2023)
  37. Oral Therapy for the Treatment of Transthyretin-Related Amyloid Cardiomyopathy. Nuvolone M, Girelli M, Merlini G. Int J Mol Sci 23 16145 (2022)
  38. Recent Progress in the Development and Clinical Application of New Drugs for Transthyretin Cardiac Amyloidosis. Zhou J, Li Y, Geng J, Zhou H, Liu L, Peng X. J Cardiovasc Pharmacol 82 427-437 (2023)
  39. Transthyretin Stabilizers and Seeding Inhibitors as Therapies for Amyloid Transthyretin Cardiomyopathy. Morfino P, Aimo A, Vergaro G, Sanguinetti C, Castiglione V, Franzini M, Perrone MA, Emdin M. Pharmaceutics 15 1129 (2023)

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  3. Transthyretin deposition in articular cartilage: a novel mechanism in the pathogenesis of osteoarthritis. Akasaki Y, Reixach N, Matsuzaki T, Alvarez-Garcia O, Olmer M, Iwamoto Y, Buxbaum JN, Lotz MK. Arthritis Rheumatol 67 2097-2107 (2015)
  4. Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis. Miller M, Pal A, Albusairi W, Joo H, Pappas B, Haque Tuhin MT, Liang D, Jampala R, Liu F, Khan J, Faaij M, Park M, Chan W, Graef I, Zamboni R, Kumar N, Fox J, Sinha U, Alhamadsheh M. J Med Chem 61 7862-7876 (2018)
  5. Effects of oral amino Acid supplements on functional capacity in patients with chronic heart failure. Lombardi C, Carubelli V, Lazzarini V, Vizzardi E, Quinzani F, Guidetti F, Rovetta R, Nodari S, Gheorghiade M, Metra M. Clin Med Insights Cardiol 8 39-44 (2014)
  6. Amyloidogenic and non-amyloidogenic transthyretin variants interact differently with human cardiomyocytes: insights into early events of non-fibrillar tissue damage. Manral P, Reixach N. Biosci Rep 35 e00172 (2015)
  7. First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers. Fox JC, Hellawell JL, Rao S, O'Reilly T, Lumpkin R, Jernelius J, Gretler D, Sinha U. Clin Pharmacol Drug Dev 9 115-129 (2020)
  8. Human TTR conformation altered by rhenium tris-carbonyl derivatives. Ciccone L, Policar C, Stura EA, Shepard W. J Struct Biol 195 353-364 (2016)
  9. Quantification of quaternary structure stability in aggregation-prone proteins under physiological conditions: the transthyretin case. Robinson LZ, Reixach N. Biochemistry 53 6496-6510 (2014)
  10. The flavonoid luteolin, but not luteolin-7-O-glucoside, prevents a transthyretin mediated toxic response. Iakovleva I, Begum A, Pokrzywa M, Walfridsson M, Sauer-Eriksson AE, Olofsson A. PLoS One 10 e0128222 (2015)
  11. Tetrabromobisphenol A Is an Efficient Stabilizer of the Transthyretin Tetramer. Iakovleva I, Begum A, Brännström K, Wijsekera A, Nilsson L, Zhang J, Andersson PL, Sauer-Eriksson AE, Olofsson A. PLoS One 11 e0153529 (2016)
  12. Blinded potency comparison of transthyretin kinetic stabilisers by subunit exchange in human plasma. Nelson LT, Paxman RJ, Xu J, Webb B, Powers ET, Kelly JW. Amyloid 28 24-29 (2021)
  13. CHF5074 (CSP-1103) stabilizes human transthyretin in mice humanized at the transthyretin and retinol-binding protein loci. Mu Y, Jin S, Shen J, Sugano A, Takaoka Y, Qiang L, Imbimbo BP, Yamamura K, Li Z. FEBS Lett 589 849-856 (2015)
  14. Comparative study of the stabilities of synthetic in vitro and natural ex vivo transthyretin amyloid fibrils. Raimondi S, Mangione PP, Verona G, Canetti D, Nocerino P, Marchese L, Piccarducci R, Mondani V, Faravelli G, Taylor GW, Gillmore JD, Corazza A, Pepys MB, Giorgetti S, Bellotti V. J Biol Chem 295 11379-11387 (2020)
  15. A cell-based high-throughput screening method to directly examine transthyretin amyloid fibril formation at neutral pH. Ueda M, Okada M, Mizuguchi M, Kluve-Beckerman B, Kanenawa K, Isoguchi A, Misumi Y, Tasaki M, Ueda A, Kanai A, Sasaki R, Masuda T, Inoue Y, Nomura T, Shinriki S, Shuto T, Kai H, Yamashita T, Matsui H, Benson MD, Ando Y. J Biol Chem 294 11259-11275 (2019)
  16. Advances in Treatment of ATTRv Amyloidosis: State of the Art and Future Prospects. Russo M, Gentile L, Toscano A, Aguennouz M, Vita G, Mazzeo A. Brain Sci 10 E952 (2020)
  17. Biophysical characterization and modulation of Transthyretin Ala97Ser. Liu YT, Yen YJ, Ricardo F, Chang Y, Wu PH, Huang SJ, Lin KP, Yu TY. Ann Clin Transl Neurol 6 1961-1970 (2019)
  18. A novel bis-furan scaffold for transthyretin stabilization and amyloid inhibition. Simões CJV, Almeida ZL, Costa D, Jesus CSH, Cardoso AL, Almeida MR, Saraiva MJ, Pinho E Melo TMVD, Brito RMM. Eur J Med Chem 121 823-840 (2016)
  19. Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities. Cioffi CL, Muthuraman P, Raja A, Varadi A, Racz B, Petrukhin K. J Med Chem 63 11054-11084 (2020)
  20. Hydrophilic Small Molecules That Harness Transthyretin To Enhance the Safety and Efficacy of Targeted Chemotherapeutic Agents. Pal A, Albusairi W, Liu F, Tuhin MTH, Miller M, Liang D, Joo H, Amin TU, Wilson EA, Faridi JS, Park M, Alhamadsheh MM. Mol Pharm 16 3237-3252 (2019)
  21. Modifications of the 7-Hydroxyl Group of the Transthyretin Ligand Luteolin Provide Mechanistic Insights into Its Binding Properties and High Plasma Specificity. Nilsson L, Larsson A, Begum A, Iakovleva I, Carlsson M, Brännström K, Sauer-Eriksson AE, Olofsson A. PLoS One 11 e0153112 (2016)
  22. Comment Targeted Therapeutics for Transthyretin Cardiac Amyloidosis. Shah SJ. Circulation 139 444-447 (2019)
  23. Stabilization of glucose-6-phosphate dehydrogenase oligomers enhances catalytic activity and stability of clinical variants. Garcia AA, Mathews II, Horikoshi N, Matsui T, Kaur M, Wakatsuki S, Mochly-Rosen D. J Biol Chem 298 101610 (2022)
  24. Tafamidis for transthyretin amyloid cardiomyopathy: the solution or just the beginning of the end? Falk RH. Eur Heart J 40 1009-1012 (2019)
  25. CSP-1103 (CHF5074) stabilizes human transthyretin in healthy human subjects. Qiang L, Guan Y, Li X, Liu L, Mu Y, Sugano A, Takaoka Y, Sakaeda T, Imbimbo BP, Yamamura KI, Jin S, Li Z. Amyloid 24 42-51 (2017)
  26. Disease-associated mutations impacting BC-loop flexibility trigger long-range transthyretin tetramer destabilization and aggregation. Esperante SA, Varejāo N, Pinheiro F, Sant'Anna R, Luque-Ortega JR, Alfonso C, Sora V, Papaleo E, Rivas G, Reverter D, Ventura S. J Biol Chem 297 101039 (2021)
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  28. A molecular basis for tetramer destabilization and aggregation of transthyretin Ala97Ser. Wang YS, Huang CH, Liou GG, Hsueh HW, Liang CT, Tseng HC, Huang SJ, Chao CC, Hsieh ST, Tzeng SR. Protein Sci 32 e4610 (2023)
  29. Development of a Highly Potent Transthyretin Amyloidogenesis Inhibitor: Design, Synthesis, and Evaluation. Pinheiro F, Pallarès I, Peccati F, Sánchez-Morales A, Varejão N, Bezerra F, Ortega-Alarcon D, Gonzalez D, Osorio M, Navarro S, Velázquez-Campoy A, Almeida MR, Reverter D, Busqué F, Alibés R, Sodupe M, Ventura S. J Med Chem 65 14673-14691 (2022)
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  31. Cardiac amyloidosis: state-of-the-art review. Bukhari S. J Geriatr Cardiol 20 361-375 (2023)
  32. Clinical and biochemical characterization of hereditary transthyretin amyloidosis caused by E61K mutation. Chu X, Wang M, Tang R, Huang Y, Yu J, Cao Y, Zheng Y, Xie Z, Deng J, Wang Z, Ma W, Song W, Wu Y, Lv H, Zhang W, Wang Z, Yuan Y, Liu Y, Meng L. Front Mol Neurosci 15 1003303 (2022)
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