Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTYRL6O)

• DTT Name: Glucocorticoid receptor (NR3C1)
• Synonyms: Nuclear receptor subfamily 3 group C member 1; GRL; GR
• Gene Name: NR3C1
• DTT Type: Successful target; [1]
• BioChemical Class: Nuclear hormone receptor
• UniProt ID: GCR_HUMAN
• TTD ID: T40016
• Sequence:
  MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
  LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLK
  LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGN
  VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGN
  SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTV
  YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVG
  SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKL
  CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRK
  CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIE
  PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSW
  MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSY
  EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTK
  LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK
• 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. 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 (By similarity).
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway: BMAL1 (R-HSA-1368108)

Molecular Interaction Atlas (MIA) of This DTT

21 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Betamethasone	DMAHJEF	Acute adrenal insufficiency		Approved	[2]
Betamethasone Benzoate	DMRMS1A	Inflammation	1A00-CA43.1	Approved	[3]
Betamethasone Valerate	DMMIAXO	Dermatological disease	DA24.Y	Approved	[3]
Budesonide	DMJIBAW	Allergic rhinitis	CA08.0	Approved	[1]
Deflazacort	DMV0RNS	Duchenne dystrophy	8C70	Approved	[3]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[4]
Dexamethasone sodium phosphate	DMIG8DW	Ataxia-telangiectasia	4A01.31	Approved	[5]
Flunisolide	DMZSWQC	Allergic rhinitis	CA08.0	Approved	[6]
Fluocinolone Acetonide	DMG2KI4	Choroiditis		Approved	[3]
Fluorometholone	DM2HKC4	Chronic obstructive pulmonary disease	CA22	Approved	[7]
Fluticasone	DMGCSVF	Allergic rhinitis	CA08.0	Approved	[8]
GW685698X	DML72VJ	Allergic rhinitis	CA08.0	Approved	[9]
Hydrocortamate	DM8K1XO	Inflammation	1A00-CA43.1	Approved	[3]
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[3]
Meprednisone	DMTL9IP	Chronic obstructive pulmonary disease	CA22	Approved	[3]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[3]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[10]
Mometasone	DM45OJN	Allergic asthma	CA23.0	Approved	[11]
Prednisolone	DMQ8FR2	Acute adrenal insufficiency		Approved	[12]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[13]
Triamcinolone	DM98IXF	Acute adrenal insufficiency		Approved	[3]

17 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CORT-125134	DMBS3UG	Cushing disease	5A70	Phase 3	[14]
FST-201	DM1YVLM	Otitis externa	AA00-AA13	Phase 3	[15]
Mapracorat	DMR23M1	Ocular disease	1F00.1Z	Phase 3	[16]
TLC599	DMGZXIQ	Knee osteoarthritis	FA01	Phase 3	[17]
BAY 86-5044	DMRZLU4	Breast cancer	2C60-2C65	Phase 2	[18]
CORT113176	DMK6IIN	Amyotrophic lateral sclerosis	8B60.0	Phase 2	[19]
DE-110	DMCQL5I	Xerophthalmia	5B55.Y	Phase 2	[20]
ETIPREDNOL DICLOACETATE	DM68K39	Rhinitis	FA20	Phase 2	[21]
GW-870086-X	DM489FT	Asthma	CA23	Phase 2	[22]
IONIS-GCCRRX	DMWV2N1	Type-2 diabetes	5A11	Phase 2	[23]
LAS-41002	DM3WY0B	Eczema	EA80-EA89	Phase 2	[24]
ORG 34517/34850	DMR3P98	Mood disorder	6A60-6E23	Phase 2	[25]
ORG-34517	DMIO59F	Depression	6A70-6A7Z	Phase 2	[26]
TPI-1020	DMSA2LZ	Chronic obstructive pulmonary disease	CA22	Phase 2	[27]
IBI-20089	DMYBHIR	Diabetic macular edema	9B71.02	Phase 1	[23]
NCX-1015	DMKJRQS	Rheumatoid arthritis	FA20	Phase 1	[28]
PT-150	DMJVPHA	Alcohol use disorder	6C40.2	Phase 1	[29]

6 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD-5423	DME8KQW	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[30]
GSK870086	DM8J30W	Asthma	CA23	Discontinued in Phase 2	[31]
NM-135	DMVH3I7	Dermatitis	EA80-EA89	Discontinued in Phase 2	[32]
WC-3027	DMLA4DU	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[33]
PF-251802	DM2V7WH	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[34]
Org-34116	DMB0IQT	Anxiety disorder	6B00-6B0Z	Terminated	[35]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
B-Octylglucoside	DMMO75G	Discovery agent	N.A.	Investigative	[36]
Hexane-1,6-Diol	DMWAPGI	Discovery agent	N.A.	Investigative	[36]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Major depressive disorder	6A20	Pre-frontal cortex	7.57E-01	-0.04	-0.07
Chronic obstructive pulmonary disease	CA23	Lung tissue	2.10E-01	-0.16	-0.49
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	5.12E-03	-0.12	-0.32
Asthma	CA23	Nasal and bronchial airway	5.51E-01	4.82E-03	6.42E-03
Atopic dermatitis	EA90	Skin	3.81E-10	-0.49	-2.7
Rheumatoid arthritis	FA20	Synovial tissue	3.40E-03	-0.15	-1.01

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