Target Information
Target General Information | Top | |||||
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Target ID |
T03818
(Former ID: TTDR01386)
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Target Name |
PPAR-gamma messenger RNA (PPARG mRNA)
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Synonyms |
Transcription factor PPAR gamma receptor (mRNA); Peroxisome proliferator-activated receptor gamma (mRNA); PPARgamma (mRNA); PPAR-gamma (mRNA); Nuclear receptor subfamily 1 group C member 3 (mRNA); NR1C3 (mRNA)
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Gene Name |
PPARG
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Target Type |
Literature-reported target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Sjogren syndrome [ICD-11: 4A43] | |||||
Function |
Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels. Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids.
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BioChemical Class |
mRNA target
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UniProt ID | ||||||
Sequence |
MGETLGDSPIDPESDSFTDTLSANISQEMTMVDTEMPFWPTNFGISSVDLSVMEDHSHSF
DIKPFTTVDFSSISTPHYEDIPFTRTDPVVADYKYDLKLQEYQSAIKVEPASPPYYSEKT QLYNKPHEEPSNSLMAIECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLIYDRCDLNC RIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEISSDIDQLNPESADLR ALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMGEDKIKFKHITPLQE QSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLLKYGVHEIIYTMLAS LMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALELDDSDLAIFIAVII LSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQKMTDLRQIVTEHVQL LQVIKKTETDMSLHPLLQEIYKDLY Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Bardoxolone methyl | Drug Info | Phase 3 | Mixed connective tissue disease | [2] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | AD-5075 | Drug Info | Terminated | Type-2 diabetes | [3], [4] | |
Mode of Action | [+] 3 Modes of Action | + | ||||
Antagonist | [+] 2 Antagonist drugs | + | ||||
1 | Bardoxolone methyl | Drug Info | [5] | |||
2 | T0070907 | Drug Info | [7], [28] | |||
Agonist | [+] 19 Agonist drugs | + | ||||
1 | AD-5075 | Drug Info | [4] | |||
2 | AD-5061 | Drug Info | [8] | |||
3 | BADGE | Drug Info | [9] | |||
4 | COOH | Drug Info | [12] | |||
5 | DRF 2519 | Drug Info | [13] | |||
6 | GW0072 | Drug Info | [15] | |||
7 | GW1929 | Drug Info | [16] | |||
8 | L-764406 | Drug Info | [20] | |||
9 | L-783483 | Drug Info | [21] | |||
10 | LG100754 | Drug Info | [22] | |||
11 | LY-465608 | Drug Info | [23] | |||
12 | nTzDpa | Drug Info | [24] | |||
13 | PAT5A | Drug Info | [25] | |||
14 | reglitazar | Drug Info | [27] | |||
15 | tagitinin A | Drug Info | [29] | |||
16 | tirotundin | Drug Info | [29] | |||
17 | TZD18 | Drug Info | [30] | |||
18 | [125I]SB-236636 | Drug Info | [31] | |||
19 | [3H]GW2331 | Drug Info | [32] | |||
Inhibitor | [+] 28 Inhibitor drugs | + | ||||
1 | (9Z,12E)-12-nitrooctadeca-9,12-dienoic acid | Drug Info | [6] | |||
2 | (E)-10-Nitrohexadec-9-enoic Acid | Drug Info | [6] | |||
3 | (E)-10-nitrooctadec-9-enoic acid | Drug Info | [6] | |||
4 | (E)-12-Nitrooctadec-12-enoic Acid | Drug Info | [6] | |||
5 | (E)-13-Nitrooctadec-12-enoic Acid | Drug Info | [6] | |||
6 | (E)-5-Nitrooctadec-5-enoic Acid | Drug Info | [6] | |||
7 | (E)-6-Nitrooctadec-5-enoic Acid | Drug Info | [6] | |||
8 | (E)-9-Nitrohexadec-9-enoicAcid | Drug Info | [6] | |||
9 | (E)-9-nitrooctadec-9-enoic acid | Drug Info | [6] | |||
10 | 2-chloro-5-nitro-N-phenylbenzamide | Drug Info | [7] | |||
11 | BRL-48482 | Drug Info | [10] | |||
12 | CHLOROCYCLINONE A | Drug Info | [11] | |||
13 | CHLOROCYCLINONE B | Drug Info | [11] | |||
14 | CHLOROCYCLINONE C | Drug Info | [11] | |||
15 | CHLOROCYCLINONE D | Drug Info | [11] | |||
16 | GNF-PF-2893 | Drug Info | [14] | |||
17 | GNF-PF-3037 | Drug Info | [14] | |||
18 | L-165461 | Drug Info | [19] | |||
19 | L-796449 | Drug Info | [19] | |||
20 | L-Tryptophan-L-2-aminoadipic acid | Drug Info | [7] | |||
21 | L-Tryptophan-L-arginine | Drug Info | [7] | |||
22 | L-Tryptophan-L-asparagine | Drug Info | [7] | |||
23 | L-Tryptophan-L-aspartic acid | Drug Info | [7] | |||
24 | L-Tryptophan-L-glutamine | Drug Info | [7] | |||
25 | L-Tryptophan-L-leucine | Drug Info | [7] | |||
26 | PD-068235 | Drug Info | [7] | |||
27 | Ploglitazone | Drug Info | [26] | |||
28 | SB-213068 | Drug Info | [10] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Profiles in Patients | Top | |||||
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Drug Resistance Mutation (DRM) |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Benzoyl 2-methyl indoles as selective PPARgamma modulators. Bioorg Med Chem Lett. 2005 Jan 17;15(2):357-62. | |||||
REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2701). | |||||
REF 4 | Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: binding and activation correlate with antidiabetic actions in db/db mice. Endocrinology. 1996 Oct;137(10):4189-95. | |||||
REF 5 | A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma. Mol Endocrinol. 2000 Oct;14(10):1550-6. | |||||
REF 6 | Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by nitroalkene fatty acids: importance of nitration position and degree ... J Med Chem. 2009 Aug 13;52(15):4631-9. | |||||
REF 7 | Tryptophan-containing dipeptide derivatives as potent PPARgamma antagonists: design, synthesis, biological evaluation, and molecular modeling. Eur J Med Chem. 2008 Dec;43(12):2699-716. | |||||
REF 8 | A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26. | |||||
REF 9 | A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J Biol Chem. 2000 Jan 21;275(3):1873-7. | |||||
REF 10 | Non thiazolidinedione antihyperglycaemic agents. 2: alpha-Carbon substituted beta-phenylpropanoic acids1, Bioorg. Med. Chem. Lett. 6(17):2127-2130 (1996). | |||||
REF 11 | Chlorocyclinones A-D, chlorinated angucyclinones from Streptomyces sp. strongly antagonizing rosiglitazone-induced PPAR-gamma activation. J Nat Prod. 2007 Dec;70(12):1934-8. | |||||
REF 12 | PPAR-gamma activation mediates adipose depot-specific effects on gene expression and lipoprotein lipase activity: mechanisms for modulation of postprandial lipemia and differential adipose accretion.Diabetes. 2003 Feb;52(2):291-9. | |||||
REF 13 | Antidiabetic and hypolipidemic potential of DRF 2519--a dual activator of PPAR-alpha and PPAR-gamma. Eur J Pharmacol. 2004 May 3;491(2-3):195-206. | |||||
REF 14 | In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. | |||||
REF 15 | A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6102-6. | |||||
REF 16 | A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes. 1999 Jul;48(7):1415-24. | |||||
REF 17 | US patent application no. 6,159,734, Antisense modulation of peroxisome proliferator-activated receptor gamma expression. | |||||
REF 18 | US patent application no. 7,425,545, Modulation of C-reactive protein expression. | |||||
REF 19 | Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80. | |||||
REF 20 | L-764406 is a partial agonist of human peroxisome proliferator-activated receptor gamma. The role of Cys313 in ligand binding. J Biol Chem. 1999 Mar 19;274(12):7913-22. | |||||
REF 21 | Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25. | |||||
REF 22 | The antidiabetic agent LG100754 sensitizes cells to low concentrations of peroxisome proliferator-activated receptor gamma ligands. J Biol Chem. 2002 Apr 12;277(15):12503-6. | |||||
REF 23 | 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. 2001 Jun 21;44(13):2061-4. | |||||
REF 24 | Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator. Mol Endocrinol. 2003 Apr;17(4):662-76. | |||||
REF 25 | Euglycemic and hypolipidemic activity of PAT5A: a unique thiazolidinedione with weak peroxisome proliferator activated receptor gamma activity. Metabolism. 2000 Nov;49(11):1417-23. | |||||
REF 26 | Peroxisome proliferator-activated receptor alpha/gamma dual agonists for the treatment of type 2 diabetes. J Med Chem. 2004 Aug 12;47(17):4118-27. | |||||
REF 27 | Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9. | |||||
REF 28 | T0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities. J Biol Chem. 2002 May 31;277(22):19649-57. | |||||
REF 29 | Sesquiterpene lactones from Tithonia diversifolia act as peroxisome proliferator-activated receptor agonists. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2954-8. | |||||
REF 30 | A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8. | |||||
REF 31 | Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma. J Pharmacol Exp Ther. 1998 Feb;284(2):751-9. | |||||
REF 32 | Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4318-23. |
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