Target Information

Target General Infomation
Target ID
T30687
Former ID
TTDR01436
Target Name
mRNA of glucocorticoid receptor
Gene Name
NR3C1
Synonyms
mRNA of GR; mRNA of GRL; mRNA of NR3C1; mRNA of Nuclear receptor subfamily 3 group C member 1; NR3C1
Target Type
Clinical Trial
Disease Atherosclerosis [ICD9: 414.0, 440; ICD10: I70]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
BioChemical Class
Zinc-finger
Target Validation
T30687
UniProt ID
P04150
Sequence
MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLK
LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGN
VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGN
SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTV
YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVG
SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKL
CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRK
CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIE
PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSW
MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSY
EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTK
LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK
Drugs and Mode of Action
Drug(s) A-348441 Drug Info Phase 1 Type 2 diabetes [528668]
ISIS-GCCR Drug Info Preclinical Type 2 diabetes [551052]
Inhibitor 1-(2,3-DICHLOROPHENYL)-2,2,2-TRIFLUORO-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (ENANTIOMERIC MIX) Drug Info [530879]
1-(3-CHLORO-4-FLUOROPHENYL)-2,2,2-TRIFLUORO-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (ENANTIOMERIC MIX) Drug Info [530879]
1-Methoxy-6-phenyl-6H-benzo[c]chromen-8-ylamine Drug Info [527034]
1-Methoxy-6-phenyl-6H-benzo[c]chromene Drug Info [527034]
2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (DIASTEREOMERIC MIX) Drug Info [530879]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one Drug Info [531079]
A-348441 Drug Info [528441]
AL-43 Drug Info [527002]
CP-394531 Drug Info [530804]
CP-409069 Drug Info [530804]
DI-O-METHYLENDIANDRIN A Drug Info [528911]
ENDIANDRIN A Drug Info [528911]
EPIERENONE Drug Info [529171]
LG-120838 Drug Info [534728]
LGD-5552 Drug Info [529166]
Methanesulfonamide derivative Drug Info [527136]
OXDEX Drug Info [530264]
RU-43044 Drug Info [530804]
WAY-214950 Drug Info [529781]
WAY-252623 Drug Info [529781]
Agonist corticosterone Drug Info [525736]
deoxycorticosterone Drug Info [525736]
RU26988 Drug Info [543901]
RU28362 Drug Info [543901]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
NetPath Pathway IL2 Signaling Pathway
TCR Signaling Pathway
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling
Signaling events mediated by HDAC Class II
FOXA2 and FOXA3 transcription factor networks
Glucocorticoid receptor regulatory network
Regulation of Androgen receptor activity
AP-1 transcription factor network
Reactome CLOCK,NPAS2 activates circadian gene expression
WikiPathways Serotonin Receptor 4/6/7 and NR3C Signaling
SIDS Susceptibility Pathways
Endoderm Differentiation
Cytodifferentiation (Part 3 of 3)
Adipogenesis
Circadian Clock
Nuclear Receptors
References
Ref 528668Liver-selective glucocorticoid receptor antagonism decreases glucose production and increases glucose disposal, ameliorating insulin resistance. Metabolism. 2007 Mar;56(3):380-7.
Ref 551052Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
Ref 525736Functional probing of the human glucocorticoid receptor steroid-interacting surface by site-directed mutagenesis. Gln-642 plays an important role in steroid recognition and binding. J Biol Chem. 2000Jun 23;275(25):19041-9.
Ref 527002Bioorg Med Chem Lett. 2004 Apr 5;14(7):1721-7.Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators.
Ref 527034Bioorg Med Chem Lett. 2004 May 3;14(9):2079-82.Synthesis and biological evaluation of novel, selective, nonsteroidal glucocorticoid receptor antagonists.
Ref 527136Bioorg Med Chem Lett. 2004 Aug 16;14(16):4179-83.Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator.
Ref 528441Bioorg Med Chem Lett. 2006 Dec 1;16(23):6086-90. Epub 2006 Sep 20.Synthesis and activity of novel bile-acid conjugated glucocorticoid receptor antagonists.
Ref 528911J Nat Prod. 2007 Jul;70(7):1118-21. Epub 2007 Jun 21.Endiandrin A, a potent glucocorticoid receptor binder isolated from the Australian plant Endiandra anthropophagorum.
Ref 529166Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9. Epub 2007 Nov 21.Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile.
Ref 529171J Med Chem. 2007 Dec 27;50(26):6443-5. Epub 2007 Nov 27.(S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: a potent, nonsteroidal, functional antagonist of themineralocorticoid receptor.
Ref 529781J Med Chem. 2008 Nov 27;51(22):7161-8.Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic triglyceride synthesis.
Ref 530264J Med Chem. 2009 Aug 13;52(15):4604-12.Investigation of the relative cellular permeability of DNA-binding pyrrole-imidazole polyamides.
Ref 530804J Med Chem. 2010 Apr 22;53(8):3065-74.Virtual screening for the identification of novel nonsteroidal glucocorticoid modulators.
Ref 530879Bioorg Med Chem Lett. 2010 May 15;20(10):3017-20. Epub 2010 Apr 11.5-Functionalized indazoles as glucocorticoid receptor agonists.
Ref 531079J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential.
Ref 534728J Med Chem. 1998 Oct 22;41(22):4354-9.5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal human progesterone receptor agonists.
Ref 543901(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. (Target id: 625).
Ref 551052Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).