Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors
Progress in understanding peroxisome proliferator-activated receptor (PPAR) subtypes as nuclear receptors that have pleiotropic effects on biological responses has enabled the exploration of new subtype-selective PPAR ligands. Such ligands are useful chemical biology/pharmacological tools to investi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9223 |
| _version_ | 1797521386619535360 |
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| author | Hiroyuki Miyachi |
| author_facet | Hiroyuki Miyachi |
| author_sort | Hiroyuki Miyachi |
| collection | DOAJ |
| description | Progress in understanding peroxisome proliferator-activated receptor (PPAR) subtypes as nuclear receptors that have pleiotropic effects on biological responses has enabled the exploration of new subtype-selective PPAR ligands. Such ligands are useful chemical biology/pharmacological tools to investigate the functions of PPARs and are also candidate drugs for the treatment of PPAR-mediated diseases, such as metabolic syndrome, inflammation and cancer. This review summarizes our medicinal chemistry research of more than 20 years on the design, synthesis, and pharmacological evaluation of subtype-selective PPAR agonists, which has been based on two working hypotheses, the ligand superfamily concept and the helix 12 (H12) holding induction concept. X-ray crystallographic analyses of our agonists complexed with each PPAR subtype validate our working hypotheses. |
| first_indexed | 2024-03-10T08:11:52Z |
| format | Article |
| id | doaj.art-986a837ee422492b9fe056e4c89fa662 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:11:52Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-986a837ee422492b9fe056e4c89fa6622023-11-22T10:40:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217922310.3390/ijms22179223Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated ReceptorsHiroyuki Miyachi0Lead Exploration Unit, Drug Discovery Initiative, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, JapanProgress in understanding peroxisome proliferator-activated receptor (PPAR) subtypes as nuclear receptors that have pleiotropic effects on biological responses has enabled the exploration of new subtype-selective PPAR ligands. Such ligands are useful chemical biology/pharmacological tools to investigate the functions of PPARs and are also candidate drugs for the treatment of PPAR-mediated diseases, such as metabolic syndrome, inflammation and cancer. This review summarizes our medicinal chemistry research of more than 20 years on the design, synthesis, and pharmacological evaluation of subtype-selective PPAR agonists, which has been based on two working hypotheses, the ligand superfamily concept and the helix 12 (H12) holding induction concept. X-ray crystallographic analyses of our agonists complexed with each PPAR subtype validate our working hypotheses.https://www.mdpi.com/1422-0067/22/17/9223peroxisome proliferator-activated receptorPPAR agoniststructural biologyligand superfamily concepthelix 12 holding induction concept |
| spellingShingle | Hiroyuki Miyachi Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors International Journal of Molecular Sciences peroxisome proliferator-activated receptor PPAR agonist structural biology ligand superfamily concept helix 12 holding induction concept |
| title | Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors |
| title_full | Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors |
| title_fullStr | Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors |
| title_full_unstemmed | Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors |
| title_short | Structural Biology-Based Exploration of Subtype-Selective Agonists for Peroxisome Proliferator-Activated Receptors |
| title_sort | structural biology based exploration of subtype selective agonists for peroxisome proliferator activated receptors |
| topic | peroxisome proliferator-activated receptor PPAR agonist structural biology ligand superfamily concept helix 12 holding induction concept |
| url | https://www.mdpi.com/1422-0067/22/17/9223 |
| work_keys_str_mv | AT hiroyukimiyachi structuralbiologybasedexplorationofsubtypeselectiveagonistsforperoxisomeproliferatoractivatedreceptors |