Target Information
| Target General Infomation | |||||
|---|---|---|---|---|---|
| Target ID |
T30687
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| Former ID |
TTDR01436
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| Target Name |
mRNA of glucocorticoid receptor
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| Gene Name |
NR3C1
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| Synonyms |
mRNA of GR; mRNA of GRL; mRNA of NR3C1; mRNA of Nuclear receptor subfamily 3 group C member 1; NR3C1
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| Target Type |
Clinical Trial
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| 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.
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| BioChemical Class |
Zinc-finger
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| Target Validation |
T30687
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| UniProt ID | |||||
| Sequence |
MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLK LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGN VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGN SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTV YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVG SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKL CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRK CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIE PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSW MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSY EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTK LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK |
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| Drugs and Mode of Action | |||||
| Drug(s) | A-348441 | Drug Info | Phase 1 | Type 2 diabetes | [1] |
| ISIS-GCCR | Drug Info | Preclinical | Type 2 diabetes | [2] | |
| Inhibitor | 1-(2,3-DICHLOROPHENYL)-2,2,2-TRIFLUORO-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (ENANTIOMERIC MIX) | Drug Info | [3] | ||
| 1-(3-CHLORO-4-FLUOROPHENYL)-2,2,2-TRIFLUORO-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (ENANTIOMERIC MIX) | Drug Info | [3] | |||
| 1-Methoxy-6-phenyl-6H-benzo[c]chromen-8-ylamine | Drug Info | [4] | |||
| 1-Methoxy-6-phenyl-6H-benzo[c]chromene | Drug Info | [4] | |||
| 2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (DIASTEREOMERIC MIX) | Drug Info | [3] | |||
| 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [5] | |||
| A-348441 | Drug Info | [6] | |||
| AL-43 | Drug Info | [7] | |||
| CP-394531 | Drug Info | [8] | |||
| CP-409069 | Drug Info | [8] | |||
| DI-O-METHYLENDIANDRIN A | Drug Info | [9] | |||
| ENDIANDRIN A | Drug Info | [9] | |||
| EPIERENONE | Drug Info | [10] | |||
| LG-120838 | Drug Info | [11] | |||
| LGD-5552 | Drug Info | [12] | |||
| Methanesulfonamide derivative | Drug Info | [13] | |||
| OXDEX | Drug Info | [14] | |||
| RU-43044 | Drug Info | [8] | |||
| WAY-214950 | Drug Info | [15] | |||
| WAY-252623 | Drug Info | [15] | |||
| Agonist | corticosterone | Drug Info | [16] | ||
| deoxycorticosterone | Drug Info | [16] | |||
| RU26988 | Drug Info | [17] | |||
| RU28362 | Drug Info | [17] | |||
| 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 1 | Liver-selective glucocorticoid receptor antagonism decreases glucose production and increases glucose disposal, ameliorating insulin resistance. Metabolism. 2007 Mar;56(3):380-7. | ||||
| REF 2 | Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011). | ||||
| REF 3 | Bioorg Med Chem Lett. 2010 May 15;20(10):3017-20. Epub 2010 Apr 11.5-Functionalized indazoles as glucocorticoid receptor agonists. | ||||
| REF 4 | Bioorg Med Chem Lett. 2004 May 3;14(9):2079-82.Synthesis and biological evaluation of novel, selective, nonsteroidal glucocorticoid receptor antagonists. | ||||
| REF 5 | J 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 6 | Bioorg 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 7 | Bioorg Med Chem Lett. 2004 Apr 5;14(7):1721-7.Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators. | ||||
| REF 8 | J Med Chem. 2010 Apr 22;53(8):3065-74.Virtual screening for the identification of novel nonsteroidal glucocorticoid modulators. | ||||
| REF 9 | J 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 10 | J 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 11 | J 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 12 | Proc 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 13 | Bioorg Med Chem Lett. 2004 Aug 16;14(16):4179-83.Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator. | ||||
| REF 14 | J Med Chem. 2009 Aug 13;52(15):4604-12.Investigation of the relative cellular permeability of DNA-binding pyrrole-imidazole polyamides. | ||||
| REF 15 | J 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 16 | Functional 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 17 | (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). | ||||
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