Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTT2SVW)

DTT Name PPAR-gamma messenger RNA (PPARG mRNA)
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)
Gene Name PPARG
DTT Type
Literature-reported target
 [1]
BioChemical Class
mRNA target
UniProt ID
PPARG_HUMAN
TTD ID
T03818
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGETLGDSPIDPESDSFTDTLSANISQEMTMVDTEMPFWPTNFGISSVDLSVMEDHSHSF
DIKPFTTVDFSSISTPHYEDIPFTRTDPVVADYKYDLKLQEYQSAIKVEPASPPYYSEKT
QLYNKPHEEPSNSLMAIECRVCGDKASGFHYGVHACEGCKGFFRRTIRLKLIYDRCDLNC
RIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEISSDIDQLNPESADLR
ALAKHLYDSYIKSFPLTKAKARAILTGKTTDKSPFVIYDMNSLMMGEDKIKFKHITPLQE
QSKEVAIRIFQGCQFRSVEAVQEITEYAKSIPGFVNLDLNDQVTLLKYGVHEIIYTMLAS
LMNKDGVLISEGQGFMTREFLKSLRKPFGDFMEPKFEFAVKFNALELDDSDLAIFIAVII
LSGDRPGLLNVKPIEDIQDNLLQALELQLKLNHPESSQLFAKLLQKMTDLRQIVTEHVQL
LQVIKKTETDMSLHPLLQEIYKDLY
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.
KEGG Pathway
PPAR signaling pathway (hsa03320 )
AMPK signaling pathway (hsa04152 )
Osteoclast differentiation (hsa04380 )
Huntington's disease (hsa05016 )
Pathways in cancer (hsa05200 )
Transcriptional misregulation in cancer (hsa05202 )
Thyroid cancer (hsa05216 )
Reactome Pathway
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
Nuclear Receptor transcription pathway (R-HSA-383280 )
PPARA activates gene expression (R-HSA-1989781 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Bardoxolone methyl DMODA2X Mixed connective tissue disease 4A43.3 Phase 3 [2]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AD-5075 DM1SLJ9 Type-2 diabetes 5A11 Terminated [3]
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51 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(9Z,12E)-12-nitrooctadeca-9,12-dienoic acid DM2REIN Discovery agent N.A. Investigative [4]
(E)-10-Nitrohexadec-9-enoic Acid DMO38CP Discovery agent N.A. Investigative [4]
(E)-10-nitrooctadec-9-enoic acid DMTF7JA Discovery agent N.A. Investigative [4]
(E)-12-Nitrooctadec-12-enoic Acid DMBQTZL Discovery agent N.A. Investigative [4]
(E)-13-Nitrooctadec-12-enoic Acid DMF74GJ Discovery agent N.A. Investigative [4]
(E)-5-Nitrooctadec-5-enoic Acid DMJKOFW Discovery agent N.A. Investigative [4]
(E)-6-Nitrooctadec-5-enoic Acid DMACVNM Discovery agent N.A. Investigative [4]
(E)-9-Nitrohexadec-9-enoicAcid DMULW35 Discovery agent N.A. Investigative [4]
(E)-9-nitrooctadec-9-enoic acid DMWC2F9 Discovery agent N.A. Investigative [4]
2-chloro-5-nitro-N-phenylbenzamide DMUGQIV Discovery agent N.A. Investigative [5]
AD-5061 DM5WV13 Discovery agent N.A. Investigative [6]
BADGE DMCK5DG Discovery agent N.A. Investigative [7]
BRL-48482 DMT4NM5 Discovery agent N.A. Investigative [8]
CHLOROCYCLINONE A DMZA394 Discovery agent N.A. Investigative [9]
CHLOROCYCLINONE B DMO78QB Discovery agent N.A. Investigative [9]
CHLOROCYCLINONE C DMX2DQ5 Discovery agent N.A. Investigative [9]
CHLOROCYCLINONE D DMK7VS1 Discovery agent N.A. Investigative [9]
COOH DM5DTZR Discovery agent N.A. Investigative [10]
DRF 2519 DMTFQG3 Discovery agent N.A. Investigative [11]
GNF-PF-2893 DMLP241 Discovery agent N.A. Investigative [12]
GNF-PF-3037 DM4RZSB Discovery agent N.A. Investigative [12]
GW0072 DM3D2R4 Discovery agent N.A. Investigative [13]
GW1929 DMOV980 Discovery agent N.A. Investigative [14]
ISIS 105987 DMIGV0H Discovery agent N.A. Investigative [15]
ISIS 105989 DMFOSYU Discovery agent N.A. Investigative [15]
ISIS 105990 DM8FY3H Discovery agent N.A. Investigative [16]
ISIS 106008 DMTY6O9 Discovery agent N.A. Investigative [15]
L-165461 DMKBSGN Discovery agent N.A. Investigative [17]
L-764406 DMG5KVS Discovery agent N.A. Investigative [18]
L-783483 DM6OTGE Discovery agent N.A. Investigative [19]
L-796449 DMWTGQM Discovery agent N.A. Investigative [17]
L-Tryptophan-L-2-aminoadipic acid DMYLONS Discovery agent N.A. Investigative [5]
L-Tryptophan-L-arginine DMYU65F Discovery agent N.A. Investigative [5]
L-Tryptophan-L-asparagine DMWZMCA Discovery agent N.A. Investigative [5]
L-Tryptophan-L-aspartic acid DMVFAD5 Discovery agent N.A. Investigative [5]
L-Tryptophan-L-glutamine DMNMRHX Discovery agent N.A. Investigative [5]
L-Tryptophan-L-leucine DMPV5D0 Discovery agent N.A. Investigative [5]
LG100754 DMEK4FY Discovery agent N.A. Investigative [20]
LY-465608 DMK64AZ Discovery agent N.A. Investigative [21]
nTzDpa DMTHB2Y Discovery agent N.A. Investigative [22]
PAT5A DMRJ104 Discovery agent N.A. Investigative [23]
PD-068235 DM8QMJ1 Discovery agent N.A. Investigative [5]
Ploglitazone DM4MKIX Discovery agent N.A. Investigative [24]
reglitazar DMQ3ER0 Discovery agent N.A. Investigative [25]
SB-213068 DMUCHNP Discovery agent N.A. Investigative [8]
T0070907 DMTKSVO Discovery agent N.A. Investigative [26]
tagitinin A DM2RN0S Discovery agent N.A. Investigative [27]
tirotundin DMQ4GBO Discovery agent N.A. Investigative [27]
TZD18 DMVCHOX Discovery agent N.A. Investigative [28]
[125I]SB-236636 DM0XUPK Discovery agent N.A. Investigative [29]
[3H]GW2331 DMJT6D3 Discovery agent N.A. Investigative [30]
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⏷ Show the Full List of 51 Investigative Drug(s)

References

1 Benzoyl 2-methyl indoles as selective PPARgamma modulators. Bioorg Med Chem Lett. 2005 Jan 17;15(2):357-62.
2 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.
3 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.
4 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.
5 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.
6 A novel oxyiminoalkanoic acid derivative, TAK-559, activates human peroxisome proliferator-activated receptor subtypes. Eur J Pharmacol. 2004 Jul 8;495(1):17-26.
7 A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J Biol Chem. 2000 Jan 21;275(3):1873-7.
8 Non thiazolidinedione antihyperglycaemic agents. 2: alpha-Carbon substituted beta-phenylpropanoic acids1, Bioorg. Med. Chem. Lett. 6(17):2127-2130 (1996).
9 Chlorocyclinones A-D, chlorinated angucyclinones from Streptomyces sp. strongly antagonizing rosiglitazone-induced PPAR-gamma activation. J Nat Prod. 2007 Dec;70(12):1934-8.
10 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.
11 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.
12 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.
13 A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6102-6.
14 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.
15 US patent application no. 6,159,734, Antisense modulation of peroxisome proliferator-activated receptor gamma expression.
16 US patent application no. 7,425,545, Modulation of C-reactive protein expression.
17 Phenylacetic acid derivatives as hPPAR agonists. Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.
18 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.
19 Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem. 1999 Mar 5;274(10):6718-25.
20 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.
21 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.
22 Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator. Mol Endocrinol. 2003 Apr;17(4):662-76.
23 Euglycemic and hypolipidemic activity of PAT5A: a unique thiazolidinedione with weak peroxisome proliferator activated receptor gamma activity. Metabolism. 2000 Nov;49(11):1417-23.
24 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.
25 Pharmacological profiles of a novel oral antidiabetic agent, JTT-501, an isoxazolidinedione derivative. Eur J Pharmacol. 1999 Jan 8;364(2-3):211-9.
26 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.
27 Sesquiterpene lactones from Tithonia diversifolia act as peroxisome proliferator-activated receptor agonists. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2954-8.
28 A novel peroxisome proliferator-activated receptor alpha/gamma dual agonist demonstrates favorable effects on lipid homeostasis. Endocrinology. 2004 Apr;145(4):1640-8.
29 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.
30 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.