{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:50:17Z","timestamp":1791859817236,"version":"4.3.4"},"reference-count":210,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T00:00:00Z","timestamp":1532649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571164"],"award-info":[{"award-number":["31571164"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31271207"],"award-info":[{"award-number":["31271207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer\u2019s disease and ulcerative colitis. The three PPAR isoforms (\u03b1, \u03b2\/\u03b4 and \u03b3) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPAR\u03b1 is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia. The pharmacological activators of PPAR\u03b3 include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks. In this review, we summarize 84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases and provide a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development.<\/jats:p>","DOI":"10.3390\/ijms19082189","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T12:20:03Z","timestamp":1532694003000},"page":"2189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":132,"title":["The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development"],"prefix":"10.3390","volume":"19","author":[{"given":"Fan","family":"Hong","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China"},{"name":"Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-6040","authenticated-orcid":false,"given":"Pengfei","family":"Xu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggong","family":"Zhai","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China"},{"name":"Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1002\/jcp.25804","article-title":"The role of various peroxisome proliferator-activated receptors and their ligands in clinical practice","volume":"233","author":"Derosa","year":"2018","journal-title":"J. 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