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Target not currently curated in GtoImmuPdb
Target id: 593
Nomenclature: Peroxisome proliferator-activated receptor-α
Systematic Nomenclature: NR1C1
Gene and Protein Information | |||||
Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 468 | 22q13.31 | PPARA | peroxisome proliferator activated receptor alpha | 63 |
Mouse | 468 | 15 40.42 cM | Ppara | peroxisome proliferator activated receptor alpha | 33 |
Rat | 468 | 7q34 | Ppara | peroxisome proliferator activated receptor alpha | 27 |
Previous and Unofficial Names |
NUC1 | nuclear receptor subfamily 1 group C member 1 | PPARalpha | PPAR |
Database Links | |
Alphafold | Q07869 (Hs), P23204 (Mm), P37230 (Rn) |
CATH/Gene3D | 3.30.50.10 |
ChEMBL Target | CHEMBL239 (Hs), CHEMBL2128 (Mm), CHEMBL2129 (Rn) |
DrugBank Target | Q07869 (Hs) |
Ensembl Gene | ENSG00000186951 (Hs), ENSMUSG00000022383 (Mm), ENSRNOG00000021463 (Rn) |
Entrez Gene | 5465 (Hs), 19013 (Mm), 25747 (Rn) |
Human Protein Atlas | ENSG00000186951 (Hs) |
KEGG Gene | hsa:5465 (Hs), mmu:19013 (Mm), rno:25747 (Rn) |
OMIM | 170998 (Hs) |
Pharos | Q07869 (Hs) |
RefSeq Nucleotide | NM_001001928 (Hs), NM_001113418 (Mm), NM_011144 (Mm), NM_013196 (Rn) |
RefSeq Protein | NP_001001928 (Hs), NP_035274 (Mm), NP_037328 (Rn) |
SynPHARM |
6299 (in complex with GW409544) 7986 (in complex with GW6471) 6309 (in complex with pirinixic acid) |
UniProtKB | Q07869 (Hs), P23204 (Mm), P37230 (Rn) |
Wikipedia | PPARA (Hs) |
Selected 3D Structures | |||||||||||||
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Natural/Endogenous Ligands |
LTB4 |
pristanic acid |
8S-HETE |
Comments: LTB4, fatty acids and eisosanoids are natural ligands |
Download all structure-activity data for this target as a CSV file
Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Pterostilbene, tetradecylglycidic acid and ortylthiopropionic acid (OTP) are also known agonists [10,58]. Fenofibrate is selective for PPARα. In a cell-based reporter transactivation assay fenofibrate is active at PPARα with an EC50 of 30μM, compared to 300μM vs. PPARγ [29]. This assay does not address the contribution to functional activity made by the active metabolite of fenofibrate, fenofibric acid. |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific antagonist tables |
Immuno Process Associations | ||
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Co-binding Partners | |||
Name | Interaction | Effect | Reference |
RXR | Physical, Functional | DNA binding | 42 |
Main Co-regulators | ||||||
Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
NCOR1 | Co-repressor | No | No | No | 10,13,16 | |
MED1 | Co-activator | No | Yes | Yes | 83 | |
NCOA1 | Co-activator | No | Yes | No | 82 | |
NCOA6 | Co-activator | No | Yes | Yes | 7,81 | |
HADHA | Co-activator | No | No | No | 36 | |
SMARCA2 | Co-activator | No | No | Yes | 65 | |
NRIP1 | Co-repressor | No | Yes | Yes | 35,52,75 | |
CITED2 | Co-activator | No | Yes | Yes | 66 | |
NCOA3 | Co-activator | No | No | Yes | 53 | |
PPARGC1A | Co-activator | No | No | No | 68 | |
PPARGC1B | Co-activator | No | No | No | 68 | |
CREBBP | Co-activator | No | Yes | Yes | There are contradicting results for ligand-dependency | 15,80 |
Main Target Genes | |||||
Name | Species | Effect | Technique | Comments | References |
CPTI: carnitine palmitoyl transferase I | Human | Activated | Transient transfection | 2,50,76 | |
MCAD (medium chain acyl-coA dehydrogenase) | Rat | Activated | Transient transfection | 25 | |
Acyl-CoA oxidase | Rat | Activated | Transient transfection | 49,67 | |
Fiat ( fasting induced adipose tissue factor) | Mouse | Activated | 41 | ||
Bifunctional enzyme | Mouse | Activated | Transient transfection | 49 | |
Slc27a1 | Mouse | Activated | Transient transfection, EMSA | FATP, fatty acid transport protein | 21 |
Apolipoprotein A-II | Mouse | Activated | Transient transfection, EMSA | negative regulation of A-I | 69 |
G0/G1 switch gene 2 (G0S2) | Mouse | Activated | 78 | ||
Liver fatty acid binding protein | Mouse | Activated | 10,34 |
Tissue Distribution | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||
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Gene Expression and Pathophysiology | ||||||||||||
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1. Boubia B, Poupardin O, Barth M, Binet J, Peralba P, Mounier L, Jacquier E, Gauthier E, Lepais V, Chatar M et al.. (2018) Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate. J Med Chem, 61 (6): 2246-2265. [PMID:29446942]
2. Brandt JM, Djouadi F, Kelly DP. (1998) Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem, 273 (37): 23786-92. [PMID:9726988]
3. Brooks DA, Etgen GJ, Rito CJ, Shuker AJ, Dominianni SJ, Warshawsky AM, Ardecky R, Paterniti JR, Tyhonas J, Karanewsky DS, Kauffman RF, Broderick CL, Oldham BA, Montrose-Rafizadeh C, Winneroski LL, Faul MM, McCarthy JR. (2001) Design and synthesis of 2-methyl-2-[4-(2-[5-methyl-2-aryloxazol-4-yl]ethoxy)phenoxy]propionic acids: a new class of dual PPARalpha/gamma agonists. J Med Chem, 44 (13): 2061-4. [PMID:11405642]
4. Brown KK, Henke BR, Blanchard SG, Cobb JE, Mook R, Kaldor I, Kliewer SA, Lehmann JM, Lenhard JM, Harrington WW, Novak PJ, Faison W, Binz JG, Hashim MA, Oliver WO, Brown HR, Parks DJ, Plunket KD, Tong WQ, Menius JA, Adkison K, Noble SA, Willson TM. (1999) A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes, 48 (7): 1415-24. [PMID:10389847]
5. Brown PJ, Stuart LW, Hurley KP, Lewis MC, Winegar DA, Wilson JG, Wilkison WO, Ittoop OR, Willson TM. (2001) Identification of a subtype selective human PPARalpha agonist through parallel-array synthesis. Bioorg Med Chem Lett, 11 (9): 1225-7. [PMID:11354382]
6. Brown PJ, Winegar DA, Plunket KD, Moore LB, Lewis MC, Wilson JG, Sundseth SS, Koble CS, Wu Z, Chapman JM, Lehmann JM, Kliewer SA, Willson TM. (1999) A ureido-thioisobutyric acid (GW9578) is a subtype-selective PPARalpha agonist with potent lipid-lowering activity. J Med Chem, 42 (19): 3785-8. [PMID:10508427]
7. Caira F, Antonson P, Pelto-Huikko M, Treuter E, Gustafsson JA. (2000) Cloning and characterization of RAP250, a novel nuclear receptor coactivator. J Biol Chem, 275 (8): 5308-17. [PMID:10681503]
8. Chakrabarti R, Misra P, Vikramadithyan RK, Premkumar M, Hiriyan J, Datla SR, Damarla RK, Suresh J, Rajagopalan R. (2004) Antidiabetic and hypolipidemic potential of DRF 2519--a dual activator of PPAR-alpha and PPAR-gamma. Eur J Pharmacol, 491 (2-3): 195-206. [PMID:15140637]
9. De Filippis B, Giancristofaro A, Ammazzalorso A, D'Angelo A, Fantacuzzi M, Giampietro L, Maccallini C, Petruzzelli M, Amoroso R. (2011) Discovery of gemfibrozil analogues that activate PPARα and enhance the expression of gene CPT1A involved in fatty acids catabolism. Eur J Med Chem, 46 (10): 5218-24. [PMID:21889235]
10. Desvergne B, Wahli W. (1999) Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev, 20 (5): 649-88. [PMID:10529898]
11. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W. (1996) The PPARalpha-leukotriene B4 pathway to inflammation control. Nature, 384 (6604): 39-43. [PMID:8900274]
12. Dietz M, Mohr P, Kuhn B, Maerki HP, Hartman P, Ruf A, Benz J, Grether U, Wright MB. (2012) Comparative molecular profiling of the PPARα/γ activator aleglitazar: PPAR selectivity, activity and interaction with cofactors. ChemMedChem, 7 (6): 1101-11. [PMID:22489042]
13. DiRenzo J, Söderstrom M, Kurokawa R, Ogliastro MH, Ricote M, Ingrey S, Hörlein A, Rosenfeld MG, Glass CK. (1997) Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors. Mol Cell Biol, 17 (4): 2166-76. [PMID:9121466]
14. Doebber TW, Kelly LJ, Zhou G, Meurer R, Biswas C, Li Y, Wu MS, Ippolito MC, Chao YS, Wang PR, Wright SD, Moller DE, Berger JP. (2004) MK-0767, a novel dual PPARalpha/gamma agonist, displays robust antihyperglycemic and hypolipidemic activities. Biochem Biophys Res Commun, 318 (2): 323-8. [PMID:15120604]
15. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M. (1997) p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha. J Biol Chem, 272 (52): 33435-43. [PMID:9407140]
16. Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M. (1999) Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein. J Biol Chem, 274 (22): 15901-7. [PMID:10336495]
17. Ebdrup S, Pettersson I, Rasmussen HB, Deussen HJ, Frost Jensen A, Mortensen SB, Fleckner J, Pridal L, Nygaard L, Sauerberg P. (2003) Synthesis and biological and structural characterization of the dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist ragaglitazar. J Med Chem, 46 (8): 1306-17. [PMID:12672231]
18. Finck BN, Bernal-Mizrachi C, Han DH, Coleman T, Sambandam N, LaRiviere LL, Holloszy JO, Semenkovich CF, Kelly DP. (2005) A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes. Cell Metab, 1 (2): 133-44. [PMID:16054054]
19. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, Kelly DP. (2002) The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest, 109 (1): 121-30. [PMID:11781357]
20. Forman BM, Chen J, Evans RM. (1997) Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA, 94 (9): 4312-7. [PMID:9113986]
21. Frohnert BI, Hui TY, Bernlohr DA. (1999) Identification of a functional peroxisome proliferator-responsive element in the murine fatty acid transport protein gene. J Biol Chem, 274 (7): 3970-7. [PMID:9933587]
22. Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodríguez De Fonseca F, Rosengarth A, Luecke H, Di Giacomo B, Tarzia G, Piomelli D. (2003) Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature, 425 (6953): 90-3. [PMID:12955147]
23. Fu J, Oveisi F, Gaetani S, Lin E, Piomelli D. (2005) Oleoylethanolamide, an endogenous PPAR-alpha agonist, lowers body weight and hyperlipidemia in obese rats. Neuropharmacology, 48 (8): 1147-53. [PMID:15910890]
24. Guerre-Millo M, Rouault C, Poulain P, André J, Poitout V, Peters JM, Gonzalez FJ, Fruchart JC, Reach G, Staels B. (2001) PPAR-alpha-null mice are protected from high-fat diet-induced insulin resistance. Diabetes, 50 (12): 2809-14. [PMID:11723064]
25. Gulick T, Cresci S, Caira T, Moore DD, Kelly DP. (1994) The peroxisome proliferator-activated receptor regulates mitochondrial fatty acid oxidative enzyme gene expression. Proc Natl Acad Sci USA, 91 (23): 11012-6. [PMID:7971999]
26. Guo Q, Sahoo SP, Wang PR, Milot DP, Ippolito MC, Wu MS, Baffic J, Biswas C, Hernandez M, Lam MH, Sharma N, Han W, Kelly LJ, MacNaul KL, Zhou G, Desai R, Heck JV, Doebber TW, Berger JP, Moller DE, Sparrow CP, Chao YS, Wright SD. (2004) A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology, 145 (4): 1640-8. [PMID:14701675]
27. Göttlicher M, Widmark E, Li Q, Gustafsson JA. (1992) Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci USA, 89 (10): 4653-7. [PMID:1316614]
28. Hanke T, Cheung SY, Kilu W, Heering J, Ni X, Planz V, Schierle S, Faudone G, Friedrich M, Wanior M et al.. (2020) A Selective Modulator of Peroxisome Proliferator-Activated Receptor γ with an Unprecedented Binding Mode. J Med Chem, 63 (9): 4555-4561. [PMID:32267688]
29. Henke BR. (2004) Peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes. J Med Chem, 47 (17): 4118-27. [PMID:15293980]
30. Henke BR, Blanchard SG, Brackeen MF, Brown KK, Cobb JE, Collins JL, Harrington WW, Hashim MA, Hull-Ryde EA, Kaldor I, Kliewer SA, Lake DH, Leesnitzer LM, Lehmann JM, Lenhard JM, Orband-Miller LA, Miller JF, Mook RA, Noble SA, Oliver W, Parks DJ, Plunket KD, Szewczyk JR, Willson TM. (1998) N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents. J Med Chem, 41 (25): 5020-36. [PMID:9836620]
31. Heppner TJ, Bonev AD, Eckman DM, Gomez MF, Petkov GV, Nelson MT. (2005) Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Pharmacology, 73 (1): 15-22. [PMID:15452359]
32. Inoue I, Itoh F, Aoyagi S, Tazawa S, Kusama H, Akahane M, Mastunaga T, Hayashi K, Awata T, Komoda T, Katayama S. (2002) Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun, 290 (1): 131-9. [PMID:11779144]
33. Issemann I, Green S. (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature, 347 (6294): 645-50. [PMID:2129546]
34. Issemann I, Prince R, Tugwood J, Green S. (1992) A role for fatty acids and liver fatty acid binding protein in peroxisome proliferation?. Biochem Soc Trans, 20 (4): 824-7. [PMID:1487072]
35. Joyeux A, Cavaillès V, Balaguer P, Nicolas JC. (1997) RIP 140 enhances nuclear receptor-dependent transcription in vivo in yeast. Mol Endocrinol, 11 (2): 193-202. [PMID:9013766]
36. Juge-Aubry CE, Kuenzli S, Sanchez JC, Hochstrasser D, Meier CA. (2001) Peroxisomal bifunctional enzyme binds and activates the activation function-1 region of the peroxisome proliferator-activated receptor alpha. Biochem J, 353 (Pt 2): 253-8. [PMID:11139388]
37. Kane CD, Stevens KA, Fischer JE, Haghpassand M, Royer LJ, Aldinger C, Landschulz KT, Zagouras P, Bagley SW, Hada W et al.. (2009) Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo. Mol Pharmacol, 75 (2): 296-306. [PMID:18971326]
38. Keller H, Devchand PR, Perroud M, Wahli W. (1997) PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents. Biol Chem, 378 (7): 651-5. [PMID:9278144]
39. Keller H, Dreyer C, Medin J, Mahfoudi A, Ozato K, Wahli W. (1993) Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci USA, 90 (6): 2160-4. [PMID:8384714]
40. Kersten S, Desvergne B, Wahli W. (2000) Roles of PPARs in health and disease. Nature, 405 (6785): 421-4. [PMID:10839530]
41. Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. (1999) Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest, 103 (11): 1489-98. [PMID:10359558]
42. Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM. (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature, 358 (6389): 771-4. [PMID:1324435]
43. Kockx M, Gervois PP, Poulain P, Derudas B, Peters JM, Gonzalez FJ, Princen HM, Kooistra T, Staels B. (1999) Fibrates suppress fibrinogen gene expression in rodents via activation of the peroxisome proliferator-activated receptor-alpha. Blood, 93 (9): 2991-8. [PMID:10216095]
44. Krey G, Braissant O, L'Horset F, Kalkhoven E, Perroud M, Parker MG, Wahli W. (1997) Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Mol Endocrinol, 11 (6): 779-91. [PMID:9171241]
45. Kuwabara K, Murakami K, Todo M, Aoki T, Asaki T, Murai M, Yano J. (2004) A novel selective peroxisome proliferator-activated receptor alpha agonist, 2-methyl-c-5-[4-[5-methyl-2-(4-methylphenyl)-4-oxazolyl]butyl]-1,3-dioxane-r-2-carboxylic acid (NS-220), potently decreases plasma triglyceride and glucose levels and modifies lipoprotein profiles in KK-Ay mice. J Pharmacol Exp Ther, 309 (3): 970-7. [PMID:14982965]
46. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, Westphal H, Gonzalez FJ. (1995) Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol, 15 (6): 3012-22. [PMID:7539101]
47. Leone TC, Weinheimer CJ, Kelly DP. (1999) A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci USA, 96 (13): 7473-8. [PMID:10377439]
48. Li PP, Shan S, Chen YT, Ning ZQ, Sun SJ, Liu Q, Lu XP, Xie MZ, Shen ZF. (2006) The PPARalpha/gamma dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats. Br J Pharmacol, 148 (5): 610-8. [PMID:16751799]
49. Marcus SL, Miyata KS, Zhang B, Subramani S, Rachubinski RA, Capone JP. (1993) Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression. Proc Natl Acad Sci USA, 90 (12): 5723-7. [PMID:8390676]
50. Mascaró C, Acosta E, Ortiz JA, Marrero PF, Hegardt FG, Haro D. (1998) Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. J Biol Chem, 273 (15): 8560-3. [PMID:9535828]
51. Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J, Peters JM, Kaya G, Gonzalez FJ, Zakany J, Metzger D, Chambon P, Duboule D, Wahli W. (2001) Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPARbeta mutant mice. J Cell Biol, 154 (4): 799-814. [PMID:11514592]
52. Miyata KS, McCaw SE, Meertens LM, Patel HV, Rachubinski RA, Capone JP. (1998) Receptor-interacting protein 140 interacts with and inhibits transactivation by, peroxisome proliferator-activated receptor alpha and liver-X-receptor alpha. Mol Cell Endocrinol, 146 (1-2): 69-76. [PMID:10022764]
53. Molnár F, Matilainen M, Carlberg C. (2005) Structural determinants of the agonist-independent association of human peroxisome proliferator-activated receptors with coactivators. J Biol Chem, 280 (28): 26543-56. [PMID:15888456]
54. MRC. PPARα receptor agonist. Accessed on 28/10/2014. Modified on 28/10/2014. MRC/AstraZeneca: Mechanisms of Disease Call, http://webarchive.nationalarchives.gov.uk/20120104105854/http://www.mrc.ac.uk/consumption/groups/public/documents/content/mrc008368.pdf
55. Murakami K, Ide T, Suzuki M, Mochizuki T, Kadowaki T. (1999) Evidence for direct binding of fatty acids and eicosanoids to human peroxisome proliferators-activated receptor alpha. Biochem Biophys Res Commun, 260 (3): 609-13. [PMID:10403814]
56. Murakami K, Tobe K, Ide T, Mochizuki T, Ohashi M, Akanuma Y, Yazaki Y, Kadowaki T. (1998) A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. Diabetes, 47 (12): 1841-7. [PMID:9836514]
57. Park SY, Cho YR, Finck BN, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, Wu JJ, Bennett AM, Rothermel B, Kalinowski A, Russell KS, Kim YB, Kelly DP, Kim JK. (2005) Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. Diabetes, 54 (9): 2514-24. [PMID:16123338]
58. Patel DD, Knight BL, Wiggins D, Humphreys SM, Gibbons GF. (2001) Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice. J Lipid Res, 42 (3): 328-37. [PMID:11254743]
59. Quang TH, Ngan NT, Minh CV, Kiem PV, Tai BH, Thao NP, Song SB, Kim YH. (2012) Anti-inflammatory and PPAR transactivational effects of secondary metabolites from the roots of Asarum sieboldii. Bioorg Med Chem Lett, 22 (7): 2527-33. [PMID:22381047]
60. Sahebkar A, Chew GT, Watts GF. (2014) New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease. Expert Opin Pharmacother, 15 (4): 493-503. [PMID:24428677]
61. Sakamoto J, Kimura H, Moriyama S, Imoto H, Momose Y, Odaka H, Sawada H. (2004) A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol, 495 (1): 17-26. [PMID:15219816]
62. Sakamoto J, Kimura H, Moriyama S, Odaka H, Momose Y, Sugiyama Y, Sawada H. (2000) Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone. Biochem Biophys Res Commun, 278 (3): 704-11. [PMID:11095972]
63. Sher T, Yi HF, McBride OW, Gonzalez FJ. (1993) cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry, 32 (21): 5598-604. [PMID:7684926]
64. Shibata T, Matsui K, Nagao K, Shinkai H, Yonemori F, Wakitani K. (1999) Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol, 364 (2-3): 211-9. [PMID:9932726]
65. Surapureddi S, Yu S, Bu H, Hashimoto T, Yeldandi AV, Kashireddy P, Cherkaoui-Malki M, Qi C, Zhu YJ, Rao MS, Reddy JK. (2002) Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha -interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator. Proc Natl Acad Sci USA, 99 (18): 11836-41. [PMID:12189208]
66. Tien ES, Davis JW, Vanden Heuvel JP. (2004) Identification of the CREB-binding protein/p300-interacting protein CITED2 as a peroxisome proliferator-activated receptor alpha coregulator. J Biol Chem, 279 (23): 24053-63. [PMID:15051727]
67. Tugwood JD, Issemann I, Anderson RG, Bundell KR, McPheat WL, Green S. (1992) The mouse peroxisome proliferator activated receptor recognizes a response element in the 5' flanking sequence of the rat acyl CoA oxidase gene. EMBO J, 11 (2): 433-9. [PMID:1537328]
68. Vega RB, Huss JM, Kelly DP. (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol, 20 (5): 1868-76. [PMID:10669761]
69. Vu-Dac N, Schoonjans K, Kosykh V, Dallongeville J, Fruchart JC, Staels B, Auwerx J. (1995) Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest, 96 (2): 741-50. [PMID:7635967]
70. Willson TM, Brown PJ, Sternbach DD, Henke BR. (2000) The PPARs: from orphan receptors to drug discovery. J Med Chem, 43 (4): 527-50. [PMID:10691680]
71. Xu HE, Lambert MH, Montana VG, Plunket KD, Moore LB, Collins JL, Oplinger JA, Kliewer SA, Gampe RT, McKee DD, Moore JT, Willson TM. (2001) Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA, 98 (24): 13919-24. [PMID:11698662]
72. Xu HE, Stanley TB, Montana VG, Lambert MH, Shearer BG, Cobb JE, McKee DD, Galardi CM, Plunket KD, Nolte RT et al.. (2002) Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha. Nature, 415 (6873): 813-7. [PMID:11845213]
73. Xu Y, Mayhugh D, Saeed A, Wang X, Thompson RC, Dominianni SJ, Kauffman RF, Singh J, Bean JS, Bensch WR, Barr RJ, Osborne J, Montrose-Rafizadeh C, Zink RW, Yumibe NP, Huang N, Luffer-Atlas D, Rungta D, Maise DE, Mantlo NB. (2003) Design and synthesis of a potent and selective triazolone-based peroxisome proliferator-activated receptor alpha agonist. J Med Chem, 46 (24): 5121-4. [PMID:14613314]
74. Xu Y, Rito CJ, Etgen GJ, Ardecky RJ, Bean JS, Bensch WR, Bosley JR, Broderick CL, Brooks DA, Dominianni SJ, Hahn PJ, Liu S, Mais DE, Montrose-Rafizadeh C, Ogilvie KM, Oldham BA, Peters M, Rungta DK, Shuker AJ, Stephenson GA, Tripp AE, Wilson SB, Winneroski LL, Zink R, Kauffman RF, McCarthy JR. (2004) Design and synthesis of alpha-aryloxy-alpha-methylhydrocinnamic acids: a novel class of dual peroxisome proliferator-activated receptor alpha/gamma agonists. J Med Chem, 47 (10): 2422-5. [PMID:15115385]
75. Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, Jetten AM. (1998) Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4. J Biol Chem, 273 (18): 10948-57. [PMID:9556573]
76. Yu GS, Lu YC, Gulick T. (1998) Co-regulation of tissue-specific alternative human carnitine palmitoyltransferase Ibeta gene promoters by fatty acid enzyme substrate. J Biol Chem, 273 (49): 32901-9. [PMID:9830040]
77. Yu K, Bayona W, Kallen CB, Harding HP, Ravera CP, McMahon G, Brown M, Lazar MA. (1995) Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem, 270 (41): 23975-83. [PMID:7592593]
78. Zandbergen F, Mandard S, Escher P, Tan NS, Patsouris D, Jatkoe T, Rojas-Caro S, Madore S, Wahli W, Tafuri S, Müller M, Kersten S. (2005) The G0/G1 switch gene 2 is a novel PPAR target gene. Biochem J, 392 (Pt 2): 313-24. [PMID:16086669]
79. Zhang R, Wang A, DeAngelis A, Pelton P, Xu J, Zhu P, Zhou L, Demarest K, Murray WV, Kuo GH. (2007) Discovery of para-alkylthiophenoxyacetic acids as a novel series of potent and selective PPARdelta agonists. Bioorg Med Chem Lett, 17 (14): 3855-9. [PMID:17524639]
80. Zhou G, Cummings R, Li Y, Mitra S, Wilkinson HA, Elbrecht A, Hermes JD, Schaeffer JM, Smith RG, Moller DE. (1998) Nuclear receptors have distinct affinities for coactivators: characterization by fluorescence resonance energy transfer. Mol Endocrinol, 12 (10): 1594-604. [PMID:9773982]
81. Zhu Y, Kan L, Qi C, Kanwar YS, Yeldandi AV, Rao MS, Reddy JK. (2000) Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR. J Biol Chem, 275 (18): 13510-6. [PMID:10788465]
82. Zhu Y, Qi C, Calandra C, Rao MS, Reddy JK. (1996) Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome proliferator-activated receptor gamma. Gene Expr, 6 (3): 185-95. [PMID:9041124]
83. Zhu Y, Qi C, Jain S, Rao MS, Reddy JK. (1997) Isolation and characterization of PBP, a protein that interacts with peroxisome proliferator-activated receptor. J Biol Chem, 272 (41): 25500-6. [PMID:9325263]
84. Zomer AW, van Der Burg B, Jansen GA, Wanders RJ, Poll-The BT, van Der Saag PT. (2000) Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator-activated receptor alpha. J Lipid Res, 41 (11): 1801-7. [PMID:11060349]
1C. Peroxisome proliferator-activated receptors: Peroxisome proliferator-activated receptor-α. Last modified on 09/06/2023. Accessed on 04/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=593.