Target Information
| Target General Information | Top | |||||
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| Target ID |
T30687
(Former ID: TTDR01436)
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| Target Name |
Glucocorticoid receptor messenger RNA (GCR mRNA)
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| Synonyms |
Nuclear receptor subfamily 3 group C member 1 (mRNA); Glucocorticoid receptor (mRNA); GRL (mRNA); GR (mRNA); Alpha-A (mRNA)
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| Gene Name |
NR3C1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Muscular dystrophy ICD-11: 8C70 | |||||
| Function |
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. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. 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. Receptor for glucocorticoids (GC).
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| BioChemical Class |
mRNA target
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| UniProt ID | ||||||
| Sequence |
MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLK LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGN VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGN SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTV YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVG SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKL CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRK CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIE PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSW MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSY EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTK LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Vamorolone | Drug Info | Approved | Duchenne muscular dystrophy | [1] | |
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | CORT125281 | Drug Info | Phase 2 | Prostate cancer | [2] | |
| 2 | ISIS-GCCR | Drug Info | Phase 2 | Diabetic complication | [3] | |
| 3 | A-348441 | Drug Info | Phase 1 | Type-2 diabetes | [4] | |
| 4 | AZD9567 | Drug Info | Phase 1 | Rheumatoid arthritis | [5] | |
| 5 | ORIC-101 | Drug Info | Phase 1 | Solid tumour/cancer | [6] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 5 Agonist drugs | + | ||||
| 1 | Vamorolone | Drug Info | [1] | |||
| 2 | (11-BETA)-11,21-DIHYDROXY-PREGN-4-ENE-3,20-DIONE | Drug Info | [9] | |||
| 3 | deoxycorticosterone | Drug Info | [9] | |||
| 4 | RU26988 | Drug Info | [20] | |||
| 5 | RU28362 | Drug Info | [20] | |||
| Antagonist | [+] 2 Antagonist drugs | + | ||||
| 1 | CORT125281 | Drug Info | [6] | |||
| 2 | ORIC-101 | Drug Info | [6] | |||
| Inhibitor | [+] 18 Inhibitor drugs | + | ||||
| 1 | A-348441 | Drug Info | [8] | |||
| 2 | 1-(2,3-DICHLOROPHENYL)-2,2,2-TRIFLUORO-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (ENANTIOMERIC MIX) | Drug Info | [10] | |||
| 3 | 1-(3-CHLORO-4-FLUOROPHENYL)-2,2,2-TRIFLUORO-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (ENANTIOMERIC MIX) | Drug Info | [10] | |||
| 4 | 1-Methoxy-6-phenyl-6H-benzo[c]chromen-8-ylamine | Drug Info | [11] | |||
| 5 | 1-Methoxy-6-phenyl-6H-benzo[c]chromene | Drug Info | [11] | |||
| 6 | 2,2,2-TRIFLUORO-1-(4-FLUOROPHENYL)-1-(1-(4-FLUOROPHENYL)-1H-INDAZOL-5-YL)ETHANOL (DIASTEREOMERIC MIX) | Drug Info | [10] | |||
| 7 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [12] | |||
| 8 | AL-43 | Drug Info | [13] | |||
| 9 | CP-394531 | Drug Info | [14] | |||
| 10 | CP-409069 | Drug Info | [14] | |||
| 11 | DI-O-METHYLENDIANDRIN A | Drug Info | [15] | |||
| 12 | ENDIANDRIN A | Drug Info | [15] | |||
| 13 | Epierenone | Drug Info | [16] | |||
| 14 | LG-120838 | Drug Info | [17] | |||
| 15 | LGD-5552 | Drug Info | [18] | |||
| 16 | OXDEX | Drug Info | [19] | |||
| 17 | RU-43044 | Drug Info | [14] | |||
| 18 | WAY-214950 | Drug Info | [21] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | AZD9567 | Drug Info | [5] | |||
| 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 | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | IL2 Signaling Pathway | |||||
| 2 | TCR Signaling Pathway | |||||
| PID Pathway | [+] 6 PID Pathways | + | ||||
| 1 | Regulation of nuclear SMAD2/3 signaling | |||||
| 2 | Signaling events mediated by HDAC Class II | |||||
| 3 | FOXA2 and FOXA3 transcription factor networks | |||||
| 4 | Glucocorticoid receptor regulatory network | |||||
| 5 | Regulation of Androgen receptor activity | |||||
| 6 | AP-1 transcription factor network | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | BMAL1:CLOCK,NPAS2 activates circadian gene expression | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | Serotonin Receptor 4/6/7 and NR3C Signaling | |||||
| 2 | SIDS Susceptibility Pathways | |||||
| 3 | Endoderm Differentiation | |||||
| 4 | Hair Follicle Development: Cytodifferentiation (Part 3 of 3) | |||||
| 5 | Adipogenesis | |||||
| 6 | Circadian Clock | |||||
| 7 | Nuclear Receptors | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 215239 | |||||
| REF 2 | Clinical pipeline report, company report or official report of Corcept. | |||||
| REF 3 | ClinicalTrials.gov (NCT01968265) Safety, Tolerability and Efficacy of ISIS-GCCRRx in Type 2 Diabetes. U.S. National Institutes of Health. | |||||
| REF 4 | Liver-selective glucocorticoid receptor antagonism decreases glucose production and increases glucose disposal, ameliorating insulin resistance. Metabolism. 2007 Mar;56(3):380-7. | |||||
| REF 5 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011). | |||||
| REF 8 | Synthesis and activity of novel bile-acid conjugated glucocorticoid receptor antagonists. Bioorg Med Chem Lett. 2006 Dec 1;16(23):6086-90. | |||||
| REF 9 | 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 10 | 5-Functionalized indazoles as glucocorticoid receptor agonists. Bioorg Med Chem Lett. 2010 May 15;20(10):3017-20. | |||||
| REF 11 | Synthesis and biological evaluation of novel, selective, nonsteroidal glucocorticoid receptor antagonists. Bioorg Med Chem Lett. 2004 May 3;14(9):2079-82. | |||||
| REF 12 | 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 rec... J Med Chem. 2010 Sep 9;53(17):6386-97. | |||||
| REF 13 | Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1721-7. | |||||
| REF 14 | Virtual screening for the identification of novel nonsteroidal glucocorticoid modulators. J Med Chem. 2010 Apr 22;53(8):3065-74. | |||||
| REF 15 | Endiandrin A, a potent glucocorticoid receptor binder isolated from the Australian plant Endiandra anthropophagorum. J Nat Prod. 2007 Jul;70(7):1118-21. | |||||
| REF 16 | (S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: a potent, nonsteroidal, functional antagonist of the mine... J Med Chem. 2007 Dec 27;50(26):6443-5. | |||||
| REF 17 | 5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal human progesterone receptor agonists. J Med Chem. 1998 Oct 22;41(22):4354-9. | |||||
| REF 18 | Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9. | |||||
| REF 19 | Investigation of the relative cellular permeability of DNA-binding pyrrole-imidazole polyamides. J Med Chem. 2009 Aug 13;52(15):4604-12. | |||||
| REF 20 | 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. (Target id: 625). | |||||
| REF 21 | Indazole-based liver X receptor (LXR) modulators with maintained atherosclerotic lesion reduction activity but diminished stimulation of hepatic tr... J Med Chem. 2008 Nov 27;51(22):7161-8. | |||||
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