{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:05:50Z","timestamp":1792623950035,"version":"4.5.0"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1007\/s00210-025-03880-y","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:28:50Z","timestamp":1741652930000},"page":"9703-9720","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Unlocking the potential of THR-\u03b2 agonist therapies: resmetirom\u2019s chemistry, biology, and patent insights"],"prefix":"10.1007","volume":"398","author":[{"given":"Khushi","family":"Dahiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Palkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"3880_CR1","doi-asserted-by":"crossref","unstructured":"Abbasi L, Irfan Q, Zaidi SMM, et al (2024) Safety and efficacy of resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): a systemic review and meta-analysis. Eur J Gastroenterol Hepatol","DOI":"10.1097\/MEG.0000000000002901"},{"key":"3880_CR2","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1016\/j.jhep.2023.07.034","volume":"79","author":"L Adorini","year":"2023","unstructured":"Adorini L, Trauner M (2023) FXR agonists in NASH treatment. J Hepatol 79:1317\u20131331. https:\/\/doi.org\/10.1016\/j.jhep.2023.07.034","journal-title":"J Hepatol"},{"key":"3880_CR3","doi-asserted-by":"publisher","first-page":"102377","DOI":"10.1016\/j.clinre.2024.102377","volume":"48","author":"SA Alshehade","year":"2024","unstructured":"Alshehade SA (2024) Resmetirom\u2019s approval: Highlighting the need for comprehensive approaches in NASH therapeutics. Clin Res Hepatol Gastroenterol 48:102377. https:\/\/doi.org\/10.1016\/j.clinre.2024.102377","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"3880_CR4","doi-asserted-by":"publisher","DOI":"10.1007\/s13679-024-00582-z","author":"K Au","year":"2024","unstructured":"Au K, Zheng M-H, Lee W-J et al (2024) Resmetirom and metabolic dysfunction-associated steatohepatitis: perspectives on multidisciplinary management from global healthcare professionals. Curr Obes Rep. https:\/\/doi.org\/10.1007\/s13679-024-00582-z","journal-title":"Curr Obes Rep"},{"key":"3880_CR5","doi-asserted-by":"publisher","first-page":"867","DOI":"10.37349\/eds.2024.00078","volume":"2","author":"MM Azam","year":"2024","unstructured":"Azam MM, Mukhtar S, Haris M et al (2024) FDA\u2019s approval of resmetirom (Rezdiffra): a breakthrough in MASH management. Expl Drug Sci 2:867\u2013874","journal-title":"Expl Drug Sci"},{"key":"3880_CR6","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.clinthera.2024.05.006","volume":"46","author":"P Beninger","year":"2024","unstructured":"Beninger P (2024) Resmetirom. Clin Ther 46:515\u2013516. https:\/\/doi.org\/10.1016\/j.clinthera.2024.05.006","journal-title":"Clin Ther"},{"key":"3880_CR7","doi-asserted-by":"publisher","first-page":"13105","DOI":"10.3390\/ijms222313105","volume":"22","author":"A Caddeo","year":"2021","unstructured":"Caddeo A, Kowalik MA, Serra M et al (2021) Tg68, a novel thyroid hormone receptor?? agonist for the treatment of nafld. Int J Mol Sci 22:13105. https:\/\/doi.org\/10.3390\/ijms222313105","journal-title":"Int J Mol Sci"},{"key":"3880_CR8","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.dld.2024.03.009","volume":"56","author":"S Ciardullo","year":"2024","unstructured":"Ciardullo S, Mantovani A (2024) Resmetirom for the treatment of nonalcoholic steatohepatitis: Evaluating the robustness of available evidence. Digest Liver Dis 56:1117\u20131118. https:\/\/doi.org\/10.1016\/j.dld.2024.03.009","journal-title":"Digest Liver Dis"},{"key":"3880_CR9","unstructured":"ClinicalTrials.gov (2017a) Study Details | Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (NASH) | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT02912260. Accessed 6 Jan 2025"},{"key":"3880_CR10","unstructured":"ClinicalTrials.gov (2017b) Study Details | Radiolabeled Study to Determine the Mass Balance of [14C] MGL-3196 | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT03220165. Accessed 6 Jan 2025"},{"key":"3880_CR11","unstructured":"ClinicalTrials.gov (2019) Study Details | Bioavailability Study of MGL-3196 Tablets Compared to Capsules | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT03413124. Accessed 6 Jan 2025"},{"key":"3880_CR12","unstructured":"ClinicalTrials.gov (2020a) Study Details | Drug Interaction Study of MGL-3196 With Clopidogrel | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04671069. Accessed 6 Jan 2025"},{"key":"3880_CR13","unstructured":"ClinicalTrials.gov (2020b) Study Details | Drug Interaction Study of MGL-3196 With Pioglitazone | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04671056. Accessed 6 Jan 2025"},{"key":"3880_CR14","unstructured":"ClinicalTrials.gov (2022) Study Details | Drug Interaction Study of MGL-3196 With Rosuvastatin and Simvastatin | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT02542969. Accessed 6 Jan 2025"},{"key":"3880_CR15","unstructured":"ClinicalTrials.gov (2023a) Study Details | A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE) | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04951219. Accessed 6 Jan 2025"},{"key":"3880_CR16","unstructured":"ClinicalTrials.gov (2023b) Study Details | Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses of MGL-3196 in Subjects With Varying Degrees of Hepatic Impairment and Healthy Matched Control Subjects | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04643795. Accessed 6 Jan 2025"},{"key":"3880_CR17","unstructured":"ClinicalTrials.gov (2023c) Study Details | A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease Patients | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT04197479. Accessed 6 Jan 2025"},{"key":"3880_CR18","unstructured":"ClinicalTrials.gov (2023d) Study Details | Ascending Single-Dose Study to Evaluate VIA-3196 in Healthy Subjects | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT01367873. Accessed 6 Jan 2025"},{"key":"3880_CR19","unstructured":"ClinicalTrials.gov (2024a) Study Details | A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Multiple Oral Doses (6 Days) of 100 mg Resmetirom in Subjects With Severe Renal Impairment and in Matched Healthy Control Subjects With Normal Renal Function | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT06397872. Accessed 6 Jan 2025"},{"key":"3880_CR20","unstructured":"ClinicalTrials.gov (2024b) Study Details | A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES) | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/study\/NCT05500222. Accessed 6 Jan 2025"},{"key":"3880_CR21","unstructured":"ClinicalTrials.gov Home | ClinicalTrials.gov. https:\/\/clinicaltrials.gov\/. Accessed 27 Aug 2024"},{"key":"3880_CR22","unstructured":"Crystal form of Resmetirom and preparation method thereof (2022) CN115124515 Crystal form of Resmetirom and preparation method thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CN376479715&_cid=P11-M0KUEI-60477-1. Accessed 2 Sep 2024"},{"key":"3880_CR23","unstructured":"Crystal form of Resmetirom as well as preparation method and application of crystal form (2023) CN116171275 Crystal form of Resmetirom as well as preparation method and application of crystal form. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CN399250661&_cid=P20-M0UNIW-78032-1. Accessed 9 Sep 2024"},{"key":"3880_CR24","unstructured":"Crystal form of resmetirom PMTAUT (2022a) Crystal form of resmetirom, preparation method therefor, and use thereof - crystal pharmaceutical Suzhou Co LTD. https:\/\/www.sumobrain.com\/patents\/wipo\/Crystal-form-resmetirom-preparation-method\/WO2022052822A1.html. Accessed 2 Sep 2024"},{"key":"3880_CR25","unstructured":"Crystal form of resmetirom PMTAUT (2022b) CA3192243 Crystal form of resmetirom, preparation method therefor, and use thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CA395497029&_cid=P20-M0UNM1-81657-1. Accessed 9 Sep 2024"},{"key":"3880_CR26","unstructured":"Crystal form of resmetirom PMTAUT (2022c) AU2021341182 Crystal form of resmetirom, preparation method therefor, and use thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=AU395407567&_cid=P20-M0VD0L-67418-1. Accessed 10 Sep 2024"},{"key":"3880_CR27","unstructured":"Crystal form of resmetirom PMTAUT (2023a) EP4286377 Crystal form of resmetirom, preparation method therefor, and use thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=EP415971083&_cid=P11-M0KUM0-68314-1. Accessed 2 Sep 2024"},{"key":"3880_CR28","unstructured":"Crystal form of resmetirom PMTAUT (2023b) US20230416234 Crystal form of resmetirom, preparation method therefor, and use thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=US418327975&_cid=P20-M0VCZK-66375-1. Accessed 10 Sep 2024"},{"key":"3880_CR29","unstructured":"DrugBank (2024) Resmetirom: Uses, Interactions, Mechanism of Action | DrugBank Online. https:\/\/go.drugbank.com\/drugs\/DB12914. Accessed 27 Aug 2024"},{"key":"3880_CR30","unstructured":"Drugs and Lactation Database (LactMed\u00ae) (2024) Resmetirom. Drugs and Lactation Database (LactMed\u00ae) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development"},{"key":"3880_CR31","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.eprac.2024.04.016","volume":"30","author":"D Dutta","year":"2024","unstructured":"Dutta D, Kamrul-Hasan ABM, Mondal E et al (2024) Role of resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, in managing nonalcoholic steatohepatitis: a systematic review and meta-analysis. Endocr Pract 30:631\u2013638. https:\/\/doi.org\/10.1016\/j.eprac.2024.04.016","journal-title":"Endocr Pract"},{"key":"3880_CR32","unstructured":"FDA (2024) FDA approves first treatment for patients with liver scarring due to fatty liver disease | FDA. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease. Accessed 27 Aug 2024"},{"key":"3880_CR33","unstructured":"FDA, CDER (2024) Highlights of prescribing information, Rezdiffra (resmetirom) tablets, for oral use Initial U.S. Approval: 2024"},{"key":"3880_CR34","unstructured":"Feigh M, N\u00f8hr-Meldgaard J, Pors S, Hansen HH *** ** (n.d.) Worsening No change 1 point improvement ?2 point improvement Preclinical efficacy and clinical translatability of resmetirom and semaglutide in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH B Study outline Background & Aim"},{"key":"3880_CR35","doi-asserted-by":"publisher","DOI":"10.1177\/10600280241259528","author":"E Guirguis","year":"2024","unstructured":"Guirguis E, Dougherty J, Thornby K et al (2024) Resmetirom: The first food and drug administration-approved medication for nonalcoholic steatohepatitis (NASH). Annals Pharmacother. https:\/\/doi.org\/10.1177\/10600280241259528","journal-title":"Annals Pharmacother"},{"key":"3880_CR36","unstructured":"Harrison S (2022) Positive topline phase 3 MAESTRO-NAFLD-1 data demonstrate resmetirom was safe, well-tolerated and provided statistically significant improvements in key measures of liver and cardiovascular health"},{"key":"3880_CR37","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1002\/hep4.1657","volume":"5","author":"SA Harrison","year":"2021","unstructured":"Harrison SA, Bashir M, Moussa SE et al (2021) Effects of resmetirom on noninvasive endpoints in a 36?week phase 2 active treatment extension study in patients with NASH. Hepatol Commun 5:573\u2013588. https:\/\/doi.org\/10.1002\/hep4.1657","journal-title":"Hepatol Commun"},{"key":"3880_CR38","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/apt.17734","volume":"59","author":"SA Harrison","year":"2024","unstructured":"Harrison SA, Ratziu V, Anstee QM et al (2024) Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther 59:51\u201363. https:\/\/doi.org\/10.1111\/apt.17734","journal-title":"Aliment Pharmacol Ther"},{"key":"3880_CR39","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1038\/s41591-023-02603-1","volume":"29","author":"SA Harrison","year":"2023","unstructured":"Harrison SA, Taub R, Neff GW et al (2023) Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nat Med 29:2919\u20132928. https:\/\/doi.org\/10.1038\/s41591-023-02603-1","journal-title":"Nat Med"},{"key":"3880_CR40","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1016\/j.jacc.2022.01.023","volume":"79","author":"GK Hovingh","year":"2022","unstructured":"Hovingh GK, Klausen IC, Heggen E et al (2022) Resmetirom (MGL-3196) in patients with heterozygous familial hypercholesterolemia. J Am Coll Cardiol 79:1220\u20131222. https:\/\/doi.org\/10.1016\/j.jacc.2022.01.023","journal-title":"J Am Coll Cardiol"},{"key":"3880_CR41","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1111\/bph.15427","volume":"178","author":"A Kannt","year":"2021","unstructured":"Kannt A, Wohlfart P, Madsen AN et al (2021) Activation of thyroid hormone receptor-? improved disease activity and metabolism independent of body weight in a mouse model of non-alcoholic steatohepatitis and fibrosis. Br J Pharmacol 178:2412\u20132423. https:\/\/doi.org\/10.1111\/bph.15427","journal-title":"Br J Pharmacol"},{"key":"3880_CR42","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1053\/j.gastro.2021.04.074","volume":"161","author":"F Kanwal","year":"2021","unstructured":"Kanwal F, Shubrook JH, Younossi Z et al (2021) Preparing for the NASH Epidemic: a call to action. Gastroenterology 161:1030-1042.e8. https:\/\/doi.org\/10.1053\/j.gastro.2021.04.074","journal-title":"Gastroenterology"},{"key":"3880_CR43","doi-asserted-by":"crossref","unstructured":"Karim G, Bansal MB (2023) Resmetirom: An orally administered, smallmolecule, liver-directed, ?-selective THR agonist for the treatment of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. touchREVIEWS in Endocrinology 19:60-70","DOI":"10.17925\/EE.2023.19.1.60"},{"key":"3880_CR44","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s40265-024-02045-0","volume":"84","author":"SJ Keam","year":"2024","unstructured":"Keam SJ (2024) Resmetirom: First Approval. Drugs 84:729\u2013735. https:\/\/doi.org\/10.1007\/s40265-024-02045-0","journal-title":"Drugs"},{"key":"3880_CR45","doi-asserted-by":"publisher","first-page":"155835","DOI":"10.1016\/j.metabol.2024.155835","volume":"154","author":"M Kokkorakis","year":"2024","unstructured":"Kokkorakis M, Boutari C, Hill MA et al (2024) Resmetirom, the first approved drug for the management of metabolic dysfunction-associated steatohepatitis: Trials, opportunities, and challenges. Metabolism 154:155835","journal-title":"Metabolism"},{"key":"3880_CR46","doi-asserted-by":"publisher","first-page":"103034","DOI":"10.1016\/j.dsx.2024.103034","volume":"18","author":"MS Kuchay","year":"2024","unstructured":"Kuchay MS, Isaacs S, Misra A (2024) Intrahepatic hypothyroidism in MASLD: Role of liver-specific thyromimetics including resmetirom. Diabetes Metab Syndr Clin Res Rev 18:103034. https:\/\/doi.org\/10.1016\/j.dsx.2024.103034","journal-title":"Diabetes Metab Syndr Clin Res Rev"},{"key":"3880_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-024-00747-9","author":"H Ledford","year":"2024","unstructured":"Ledford H (2024) First US drug approved for a liver disease surging around the world. Nature. https:\/\/doi.org\/10.1038\/d41586-024-00747-9","journal-title":"Nature"},{"key":"3880_CR48","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.06.016","author":"S Lens","year":"2024","unstructured":"Lens S (2024) Resmetirom for Non-alcoholic Steatohepatitis. Gastroenterology. https:\/\/doi.org\/10.1053\/j.gastro.2024.06.016","journal-title":"Gastroenterology"},{"key":"3880_CR49","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.155935","volume":"156","author":"L-Y Lian","year":"2024","unstructured":"Lian L-Y, Targher G, Byrne CD et al (2024) Resmetirom for MASH patients with diabetes: challenges and opportunities in the real world. Metabolism 156:155935. https:\/\/doi.org\/10.1016\/j.metabol.2024.155935","journal-title":"Metabolism"},{"key":"3880_CR50","doi-asserted-by":"publisher","first-page":"22172","DOI":"10.1039\/d3ra02521g","volume":"13","author":"C Liu","year":"2023","unstructured":"Liu C, Xu Y, Yuan H et al (2023) Solubility determination, dissolution properties and solid transformation of resmetirom (form A) in heptane and seven alcohols. RSC Adv 13:22172\u201322184. https:\/\/doi.org\/10.1039\/d3ra02521g","journal-title":"RSC Adv"},{"key":"3880_CR51","unstructured":"LiverTox (2024) Resmetirom, LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National institute of diabetes and digestive and kidney diseases"},{"key":"3880_CR52","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.43635","author":"IJ Mazhar","year":"2023","unstructured":"Mazhar IJ, Yasir M, Sarfraz S et al (2023) Vitamin E and pioglitazone: a comprehensive systematic review of their efficacy in non-alcoholic fatty liver disease. Cureus. https:\/\/doi.org\/10.7759\/cureus.43635","journal-title":"Cureus"},{"key":"3880_CR53","unstructured":"Method of synthesizing thyroid hormone analogs and polymorphs thereof (2016) US9266861B2 - Method of synthesizing thyroid hormone analogs and polymorphs thereof - Google Patents. https:\/\/patents.google.com\/patent\/US9266861B2\/en. Accessed 27 Aug 2024"},{"key":"3880_CR54","unstructured":"Methods of synthesizing thyroid hormone analogs and polymorphs thereof (2019) US10376517B2 - Methods of synthesizing thyroid hormone analogs and polymorphs thereof - Google Patents. https:\/\/patents.google.com\/patent\/US10376517B2\/en. Accessed 27 Aug 2024"},{"key":"3880_CR55","unstructured":"Methods of synthesizing thyroid hormone analogs and polymorphs thereof (2023) US11564926B2 - Methods of synthesizing thyroid hormone analogs and polymorphs thereof - Google Patents. https:\/\/patents.google.com\/patent\/US11564926B2\/en. Accessed 27 Aug 2024"},{"key":"3880_CR56","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1111\/liv.15930","volume":"44","author":"S Petta","year":"2024","unstructured":"Petta S, Targher G, Romeo S et al (2024) The first MASH drug therapy on the horizon: Current perspectives of resmetirom. Liver Int 44:1526\u20131536","journal-title":"Liver Int"},{"key":"3880_CR57","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ejim.2024.04.013","volume":"124","author":"P Portincasa","year":"2024","unstructured":"Portincasa P, Baffy G (2024) Metabolic dysfunction-associated steatotic liver disease: Evolution of the final terminology. Eur J Intern Med 124:35\u201339. https:\/\/doi.org\/10.1016\/j.ejim.2024.04.013","journal-title":"Eur J Intern Med"},{"key":"3880_CR58","unstructured":"Preparation method of Resmetirom key intermediate III (2023) CN117263870 Preparation method of Resmetirom key intermediate III. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CN418706943&_cid=P11-M0KUFA-61304-1. Accessed 2 Sep 2024"},{"key":"3880_CR59","doi-asserted-by":"publisher","first-page":"4130","DOI":"10.1097\/ms9.0000000000002195","volume":"86","author":"A Raja","year":"2024","unstructured":"Raja A, Subhash Sagar R, Saeed S et al (2024) Safety and efficacy of resmetirom in the treatment of patients with non-alcoholic steatohepatitis and liver fibrosis: a systematic review and meta-analysis. Annals Med Surge 86:4130\u20134138. https:\/\/doi.org\/10.1097\/ms9.0000000000002195","journal-title":"Annals Med Surge"},{"key":"3880_CR60","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41575-024-00909-0","volume":"21","author":"K Ray","year":"2024","unstructured":"Ray K (2024) Resmetirom proves positive for NASH with liver fibrosis. Nat Rev Gastroenterol Hepatol 21:218\u2013218. https:\/\/doi.org\/10.1038\/s41575-024-00909-0","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"3880_CR61","unstructured":"Resmetirom crystal PMFSAUT (2021) WO2021129465 Resmetirom crystal, preparation method for same, and uses thereof. In: https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2021129465&_cid=P11-M0KUNG-69700-1. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2021129465&_cid=P11-M0KUNG-69700-1. Accessed 2 Sep 2024"},{"key":"3880_CR62","unstructured":"Resmetirom crystal form PMTAUT (2022a) WO2022171200 Resmetirom crystal form, preparation method therefor, and use thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2022171200&_cid=P11-M0KUI0-64126-1. Accessed 2 Sep 2024"},{"key":"3880_CR63","unstructured":"Resmetirom crystal PMFSAUT (2022b) US20220372021 Resmetirom crystal, preparation method for same, and uses thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=US379737480&_cid=P20-M0VD2A-69078-1. Accessed 10 Sep 2024"},{"key":"3880_CR64","unstructured":"Resmetirom crystal form and preparation method therefor and use thereof (2021) WO2021063367 Resmetirom crystal form and preparation method therefor and use thereof. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2021063367. Accessed 30 Aug 2024"},{"key":"3880_CR65","unstructured":"Resmetirom intermediate and preparation method thereof and preparation method of intermediate I (2023) CN117164568 Resmetirom intermediate and preparation method thereof, and preparation method of intermediate III. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CN417484714&_cid=P11-M0KUG2-62079-1. Accessed 2 Sep 2024"},{"key":"3880_CR66","unstructured":"Resmetirom intermediate and preparation method thereof and preparation method of key intermediate I (2024) CN117603149 Resmetirom intermediate and preparation method thereof, and preparation method of key intermediate III. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CN424924940&_cid=P11-M0KUGW-62965-1. Accessed 2 Sep 2024"},{"key":"3880_CR67","unstructured":"Resmetirom for reducing liver volume (2023a) CA3233319 Resmetirom for reducing liver volume. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CA426513841&_cid=P20-M0UNHT-76526-1. Accessed 9 Sep 2024"},{"key":"3880_CR68","unstructured":"Resmetirom for reducing liver volume (2023b) AU2022348966 Resmetirom for reducing liver VOLUME. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=AU426494472&_cid=P20-M0VD39-70132-1. Accessed 10 Sep 2024"},{"key":"3880_CR69","unstructured":"Resmetirom for reducing liver volume (2024a) EP4408428 Resmetirom for reducing liver volume. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=EP436341785&_cid=P20-M0UNB5-68977-1. Accessed 9 Sep 2024"},{"key":"3880_CR70","unstructured":"Resmetirom for reducing liver volume (2024b) NZ809541 Resmetirom for reducing liver volume. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=NZ428293431&_cid=P20-M0UNOC-84102-1. Accessed 9 Sep 2024"},{"key":"3880_CR71","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2024.07.002","author":"A Saeed","year":"2024","unstructured":"Saeed A, Rai KD, Saeed M (2024) Resmetirom: Breakthrough therapeutic approach for metabolic dysfunction-associated steatohepatitis. Liver Res. https:\/\/doi.org\/10.1016\/j.livres.2024.07.002","journal-title":"Liver Res"},{"key":"3880_CR72","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s13105-023-00954-4","volume":"79","author":"P Sangro","year":"2023","unstructured":"Sangro P, de la Torre Al\u00e1ez M, Sangro B, D\u2019Avola D (2023) Metabolic dysfunction-associated fatty liver disease (MAFLD): an update of the recent advances in pharmacological treatment. J Physiol Biochem 79:869\u2013879","journal-title":"J Physiol Biochem"},{"key":"3880_CR73","doi-asserted-by":"publisher","first-page":"331","DOI":"10.3389\/fmed.2020.00331","volume":"7","author":"F Saponaro","year":"2020","unstructured":"Saponaro F, Sestito S, Runfola M et al (2020) Selective Thyroid Hormone Receptor-Beta (TR?) Agonists: New Perspectives for the Treatment of Metabolic and Neurodegenerative Disorders. Front Med (Lausanne) 7:331","journal-title":"Front Med (Lausanne)"},{"key":"3880_CR74","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.livres.2024.03.002","volume":"8","author":"RA Sinha","year":"2024","unstructured":"Sinha RA (2024) Targeting nuclear receptors for NASH\/MASH: From bench to bedside. Liver Res 8:34\u201345","journal-title":"Liver Res"},{"key":"3880_CR75","unstructured":"Solid state forms of resmetirom (2022a) WO2022086894 SOLID STATE FORMS OF RESMETIROM. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2022086894. Accessed 2 Sep 2024"},{"key":"3880_CR76","unstructured":"Solid state forms of resmetirom (2022b) CA3195789 Solid state forms of resmetirom. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CA398152217&_cid=P11-M0KUDK-59486-1. Accessed 2 Sep 2024"},{"key":"3880_CR77","unstructured":"Solid state forms of resmetirom (2023) US20230364099 Solid state forms of resmetirom. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=US414442009&_cid=P20-M0UNN9-83033-1. Accessed 9 Sep 2024"},{"key":"3880_CR78","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S2468-1253(24)00049-9","volume":"9","author":"The Lancet Gastroenterology & Hepatology","year":"2024","unstructured":"The Lancet Gastroenterology & Hepatology (2024) Resmetirom for NASH: balancing promise and prudence. Lancet Gastroenterol Hepatol 9:273","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"3880_CR79","unstructured":"Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders (2022a) AU2022213405 Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=AU402874581&_cid=P20-M0VCQY-57000-1. Accessed 10 Sep 2024"},{"key":"3880_CR80","unstructured":"Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders (2022b) WO2022165227 Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=WO2022165227&_cid=P20-M0VCUH-61085-1. Accessed 10 Sep 2024"},{"key":"3880_CR81","unstructured":"Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders (2022c) CA3206392 Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CA403677711&_cid=P20-M0VCWB-63152-1. Accessed 10 Sep 2024"},{"key":"3880_CR82","unstructured":"Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders (2023a) ep4284373 Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=EP415967016&_cid=P20-M0UNW0-92129-1. Accessed 9 Sep 2024"},{"key":"3880_CR83","unstructured":"Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders (2023b) NZ801980 Therapeutic combinations of rosuvastatin and resmetirom for the treatment of liver disorders or lipid disorders. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=NZ403357540&_cid=P20-M0VCSZ-59526-1. Accessed 10 Sep 2024"},{"key":"3880_CR84","unstructured":"Therapeutic combination of rosuvastatin and RESMETIROM for treatment of liver or lipid disorders (2023c) CN116847847 Therapeutic combination of rosuvastatin and RESMETIROM for treatment of liver or lipid disorders. https:\/\/patentscope.wipo.int\/search\/en\/detail.jsf?docId=CN410660739&_cid=P11-M0KUP0-71283-1. Accessed 2 Sep 2024"},{"key":"3880_CR85","unstructured":"Thirumalai Rajan S, Eswaraiah S, Satyanarayana R, Maheshwar Reddy S (2024) A process for the preparation of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydropyridazin-3-yloxy)phenyl]-3,5-dioxo-2,3,4,5-tetrahydro[1,2,4]triazine-6-carbonitrile"},{"key":"3880_CR86","doi-asserted-by":"publisher","first-page":"120857","DOI":"10.1016\/j.molliq.2022.120857","volume":"369","author":"G Tian","year":"2023","unstructured":"Tian G, Luo Y, Lou B et al (2023) Screening, packing systematics, Hansen solubility parameters and desolvation of resmetirom (MGL-3196) solvates. J Mol Liq 369:120857. https:\/\/doi.org\/10.1016\/j.molliq.2022.120857","journal-title":"J Mol Liq"},{"key":"3880_CR87","doi-asserted-by":"publisher","first-page":"5843","DOI":"10.3390\/ijms24065843","volume":"24","author":"X Wang","year":"2023","unstructured":"Wang X, Wang L, Geng L et al (2023) Resmetirom ameliorates NASH-model mice by suppressing STAT3 and NF-?B signaling pathways in an RGS5-dependent manner. Int J Mol Sci 24:5843. https:\/\/doi.org\/10.3390\/ijms24065843","journal-title":"Int J Mol Sci"},{"key":"3880_CR88","doi-asserted-by":"publisher","first-page":"580","DOI":"10.3350\/cmh.2024.0301","volume":"30","author":"N-B Yang","year":"2024","unstructured":"Yang N-B, Seto W-K, Zheng M-H (2024) Functional cure of chronic hepatitis B encounters resmetirom. Clin Mol Hepatol 30:580\u2013581. https:\/\/doi.org\/10.3350\/cmh.2024.0301","journal-title":"Clin Mol Hepatol"},{"key":"3880_CR89","doi-asserted-by":"publisher","first-page":"969","DOI":"10.3350\/cmh.2023.0359","volume":"29","author":"ML Yeh","year":"2023","unstructured":"Yeh ML, Yu ML (2023) From nonalcoholic steatohepatitis, metabolic dys-function-associated fatty liver disease, to steatotic liver disease: Updates of nomenclature and impact on clinical trials. Clin Mol Hepatol 29:969\u2013972","journal-title":"Clin Mol Hepatol"},{"key":"3880_CR90","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.cgh.2021.07.039","volume":"20","author":"ZM Younossi","year":"2022","unstructured":"Younossi ZM, Stepanova M, Taub RA et al (2022) Hepatic fat reduction due to resmetirom in patients with nonalcoholic steatohepatitis is associated with improvement of quality of life. Clin Gastroenterol Hepatol 20:1354-1361.e7. https:\/\/doi.org\/10.1016\/j.cgh.2021.07.039","journal-title":"Clin Gastroenterol Hepatol"},{"key":"3880_CR91","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1089\/thy.2020.0071","volume":"30","author":"R Zucchi","year":"2020","unstructured":"Zucchi R (2020) Thyroid hormone analogues: An update. Thyroid 30:1099\u20131105. https:\/\/doi.org\/10.1089\/thy.2020.0071","journal-title":"Thyroid"},{"key":"3880_CR92","unstructured":"(2004) Resmetirom | C17H12Cl2N6O4 | CID 15981237 - PubChem. In: PubChem, National Library of Medicine (US), National Center for Biotechnology Information (NCBI). https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Resmetirom#section=Consolidated-References. Accessed 27 Aug 2024"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-03880-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-025-03880-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-025-03880-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T07:29:53Z","timestamp":1757143793000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-025-03880-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":92,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["3880"],"URL":"https:\/\/doi.org\/10.1007\/s00210-025-03880-y","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"assertion":[{"value":"22 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}