Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDC00073

Target Information
NameCorticotropin releasing factor receptor 1    
Type of targetClinical trial target    
SynonymsCRF receptor    
CRF-1 receptor    
CRF-R    
CRF-R1    
CRF1    
CRH-R 1    
Corticotropin-releasing hormone receptor 1    
Corticotropin-releasing hormone type 1 receptor    
DiseaseAnxiety Disorders
[ICD9: 300   ICD10: F40-F42]
[1][2]
Depression
[ICD9: 311   ICD10: F32]
[1][2]
Innate anxiety
[ICD9: 300   ICD10: F40-F42]
[3]
Irritable Bowel Syndrome (IBS)
[ICD9: 564.1   ICD10: K58]
[4][5][6]
Obesity
[ICD9: 278   ICD10: E66]
[7]
Stress-related disorders
[ICD9: 296   ICD10: F30-F39]
[8]
Drug(s)CRF-1 antagonistPhase II completedAnxiety Disorders, Irritable Bowel Syndrome (IBS)[1][2]
GSK561679Phase IIMajor Depressive Disorder (MDD) & anxiety[9]
CRF-1 antagonistPhase I completedDepression[1][2]
GSK586529Phase I completedDepression & anxiety[9]
SSR125543Phase IDepression; PTSD[10]
CP-316,311Terminated in Phase IIMajor Depressive Disorder, Severe Mood Disorders[11]
GW876008Suspended in Phase II in GSK 2008 ReportIrritable bowel syndrome (also depression & anxiety)[11]
NBI-34041Discontinued in Phase IIAnxiety Disorders, Depression, Irritable Bowel Syndrome (IBS)[4][5][6]
NBI-37582DiscontinuedAnxiety Disorders, Depression[12]
PexacerfontDiscontinued in Phase II/IIISevere Mood Disorders[11]
BioChemical ClassG-protein coupled receptor (Secretin family)    
PathwayLong-term depression
Neuroactive ligand-receptor interaction
UniProt IDP34998
PDB Structure2L27; 3EHS; 3EHT; 3EHU.    
FunctionThis is a receptor for corticotropin releasing factor. Shows high-affinity crf binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.    
SequenceMGGHPQLRLVKALLLLGLNPVSASLQDQHCESLSLASNISGLQCNASVDLIGTCWPRSPA GQLVVRPCPAFFYGVRYNTTNNGYRECLANGSWAARVNYSECQEILNEEKKSKVHYHVAV IINYLGHCISLVALLVAFVLFLRLRPGCTHWGDQADGALEVGAPWSGAPFQVRRSIRCLR NIIHWNLISAFILRNATWFVVQLTMSPEVHQSNVGWCRLVTAAYNYFHVTNFFWMFGEGC YLHTAIVLTYSTDRLRKWMFICIGWGVPFPIIVAWAIGKLYYDNEKCWFGKRPGVYTDYI YQGPMILVLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFF VNPGEDEVSRVVFIYFNSFLESFQGFFVSVFYCFLNSEVRSAIRKRWHRWQDKHSIRARV ARAMSIPTSPTRVSFHSIKQSTAV
Related US Patent6,440,960
6,500,839
6,515,005
6,541,469
6,583,143
Target ValidationClick to Find Target Validation Information.    
InhibitorBMS-561388[13]
BMS-561388[14]
CP-316311[15]
CP-376395[15]
DMP-696[16]
N-mesityl-4,6-dimethyl-3-tosylpyridin-2-amine[17]
N-mesityl-6-methyl-3-tosylpyridin-2-amine[17]
PD-171729[18]
R-121919[19]
SR-125543A[19]
AntagonistAntalarmin[20]
Antalarmin[21]
CP-154526[22]
CP-316,311[11]
CP154,526[21]
CRA1000[21]
CRA1001[21]
CRF-1 antagonist[1][2]
DMP-695/696[21]
GSK561679[9]
GSK586529[9]
GW876008[11]
NBI-27914[21]
NBI-34041[4][5][6]
NBI-37582[12]
Pexacerfont[11]
R121919[3]
R121919[21]
SSR125543[10]
SSR125543A[21]
Telavancin[21]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Dihydropyrrole[2,3-d]pyridine derivatives as novel corticotropin-releasing factor-1 antagonists: mapping of the receptor binding pocket by in silico docking studies. J Med Chem. 2008 Nov 27;51(22):7273-86. To Reference
Ref 2Development of drugs for gastrointestinal motor disorders: translating science to clinical need. Neurogastroenterol Motil. 2008 Mar;20(3):177-84. To Reference
Ref 3The CRH1 receptor antagonist R121919 attenuates stress-elicited sleep disturbances in rats, particularly in those with high innate anxiety. J Psychiatr Res. 2002 Jul-Aug;36(4):197-208. To Reference
Ref 4Central CRH system in depression and anxiety--evidence from clinical studies with CRH1 receptor antagonists. Eur J Pharmacol. 2008 Apr 7;583(2-3):350-7. Epub 2008 Jan 24. To Reference
Ref 5CRH-sub-1 receptor antagonists for the treatment of depression and anxiety. Exp Clin Psychopharmacol. 2007 Dec;15(6):519-28. To Reference
Ref 6High-affinity CRF1 receptor antagonist NBI-34041: preclinical and clinical data suggest safety and efficacy in attenuating elevated stress response. Neuropsychopharmacology. 2007 Sep;32(9):1941-9. Epub 2007 Feb 7. To Reference
Ref 7The corticotropin-releasing factor family of peptides and CRF receptors: their roles in the regulation of energy balance. Eur J Pharmacol. 2002 Apr 12;440(2-3):189-97. To Reference
Ref 8Therapeutic potential of CRF receptor antagonists: a gut-brain perspective. Expert Opin Investig Drugs. 2001 Apr;10(4):647-59. To Reference
Ref 9GSK. Product Development Pipeline. February 2009. To Reference
Ref 10Pharma & Vaccines. Product Development Pipeline. April 29 2009. To Reference
Ref 11Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2. To Reference
Ref 12CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008. To Reference
Ref 13J Med Chem. 2009 May 14;52(9):3073-83.8-(4-Methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazines: selective and centrally active corticotropin-releasing factor receptor-1 (CRF1) antagonists. To Reference
Ref 14J Med Chem. 2009 May 14;52(9):3084-92.Synthesis and structure-activity relationships of 8-(pyrid-3-yl)pyrazolo[1,5-a]-1,3,5-triazines: potent, orally bioavailable corticotropin releasing factor receptor-1 (CRF1) antagonists. To Reference
Ref 15J Med Chem. 2008 Mar 13;51(5):1385-92. Epub 2008 Feb 21.2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists. To Reference
Ref 16J Med Chem. 2009 Jul 23;52(14):4161-72.In vitro intrinsic clearance-based optimization of N3-phenylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists. To Reference
Ref 17Bioorg Med Chem Lett. 2006 Feb 15;16(4):934-7. Epub 2005 Nov 16.Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as corticotropin-releasing factor1 receptor ligands. To Reference
Ref 18Bioorg Med Chem Lett. 1998 Aug 18;8(16):2067-70.Pyrazolo[1,5-a]pyrimidine CRF-1 receptor antagonists. To Reference
Ref 19Bioorg Med Chem Lett. 2008 Aug 15;18(16):4486-90. Epub 2008 Jul 18.2-Arylpyrimidines: novel CRF-1 receptor antagonists. To Reference
Ref 20Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress. Life Sci. 1999;65(4):PL53-8. To Reference
Ref 21A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68. To Reference
Ref 22Effects of the CRH receptor antagonist CP-154,526 on intravenous cocaine self-administration in rats. Neuropsychopharmacology. 2000 Nov;23(5):577-86. To Reference



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

   
 
 
Computer-aided Drug Design
about BIDD |  databases |  software |  teaching |  research |  links

 

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543