Target Information

Target General Infomation
Target ID
T45262
Former ID
TTDC00073
Target Name
Corticotropin releasing factor receptor 1
Gene Name
CRHR1
Synonyms
CRF receptor; CRF-1 receptor; CRF-R; CRF-R1; CRF1; CRH-R 1; Corticotropin-releasing hormone receptor 1; Corticotropin-releasing hormone type 1 receptor; CRHR1
Target Type
Successful
Disease Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42]
Anxiety disorder; Depression [ICD9: 300, 311; ICD10: F30-F39, F40-F42]
Alcohol use disorders; Major depressive disorder [ICD9:303, 296.2, 296.3, 710.0; ICD10: F10.2, F32, F33, M32]
Depression; Anxiety [ICD9: 300, 311; ICD10: F30-F39, F40-F42]
Depression [ICD9: 311; ICD10: F30-F39]
Irritable bowel syndrome [ICD9: 564.1, 787.91; ICD10: A09, K58, K59.1]
Major depressive disorder; Severe mood disorder [ICD9: 296, 296.2, 296.3; ICD10: F30-F39, F32, F33]
Staphylococcus aureus infection [ICD10: B95.6]
Function
G-protein coupled receptor for CRH (corticotropin- releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.
BioChemical Class
GPCR secretin
Target Validation
T45262
UniProt ID
P34998
Sequence
MGGHPQLRLVKALLLLGLNPVSASLQDQHCESLSLASNISGLQCNASVDLIGTCWPRSPA
GQLVVRPCPAFFYGVRYNTTNNGYRECLANGSWAARVNYSECQEILNEEKKSKVHYHVAV
IINYLGHCISLVALLVAFVLFLRLRPGCTHWGDQADGALEVGAPWSGAPFQVRRSIRCLR
NIIHWNLISAFILRNATWFVVQLTMSPEVHQSNVGWCRLVTAAYNYFHVTNFFWMFGEGC
YLHTAIVLTYSTDRLRKWMFICIGWGVPFPIIVAWAIGKLYYDNEKCWFGKRPGVYTDYI
YQGPMILVLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFF
VNPGEDEVSRVVFIYFNSFLESFQGFFVSVFYCFLNSEVRSAIRKRWHRWQDKHSIRARV
ARAMSIPTSPTRVSFHSIKQSTAV
Drugs and Mode of Action
Drug(s) Telavancin Drug Info Approved Staphylococcus aureus infection [551871]
Pexacerfont Drug Info Phase 2/3 Anxiety disorder [522037]
GSK561679 Drug Info Phase 2 Alcohol use disorders; Major depressive disorder [523144]
ONO-2333Ms Drug Info Phase 2 Anxiety disorder [522084]
SSR125543 Drug Info Phase 2 Anxiety disorder [522897]
GSK586529 Drug Info Phase 1 Depression; Anxiety [522358]
CRA1000 Drug Info Preclinical Anxiety disorder [540436], [546853]
CP-316,311 Drug Info Discontinued in Phase 2 Major depressive disorder; Severe mood disorder [546625]
GW876008 Drug Info Discontinued in Phase 2 Irritable bowel syndrome [536580]
Antalarmin Drug Info Terminated Depression [540427], [546326]
DMP-696 Drug Info Terminated Anxiety disorder [540437], [546984]
NBI-37582 Drug Info Terminated Anxiety disorder; Depression [527521]
Antagonist Antalarmin Drug Info [534886]
CP-316,311 Drug Info [536580]
CP154,526 Drug Info [536307]
CRA1000 Drug Info [536307]
DMP-695/696 Drug Info [536307]
GSK561679 Drug Info [550963]
GSK586529 Drug Info [550963]
GW876008 Drug Info [536580]
NBI-27914 Drug Info [536307]
NBI-37582 Drug Info [550543]
ONO-2333Ms Drug Info [532181]
Pexacerfont Drug Info [536580]
SSR125543 Drug Info [549823]
Telavancin Drug Info [536307]
Inhibitor BMS-561388 Drug Info [530071]
CP-376395 Drug Info [529324]
DMP-696 Drug Info [530226]
N-mesityl-4,6-dimethyl-3-tosylpyridin-2-amine Drug Info [527873]
N-mesityl-6-methyl-3-tosylpyridin-2-amine Drug Info [527873]
PD-171729 Drug Info [534796]
SR-125543A Drug Info [529622]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Long-term depression
NetPath Pathway TNFalpha Signaling Pathway
PANTHER Pathway Cortocotropin releasing factor receptor signaling pathway
Reactome Class B/2 (Secretin family receptors)
G alpha (s) signalling events
WikiPathways GPCRs, Class B Secretin-like
Myometrial Relaxation and Contraction Pathways
Corticotropin-releasing hormone
GPCR ligand binding
GPCR downstream signaling
References
Ref 522037ClinicalTrials.gov (NCT00481325) Study of Pexacerfont (BMS-562086) in the Treatment of Outpatients With Generalized Anxiety Disorder. U.S. National Institutes of Health.
Ref 522084ClinicalTrials.gov (NCT00514865) Placebo-Controlled Study of ONO-2333Ms in Patients With Recurrent Major Depressive Disorder. U.S. National Institutes of Health.
Ref 522358ClinicalTrials.gov (NCT00703547) A First Time in Human Study of GSK586529 in Healthy Volunteers. U.S. National Institutes of Health.
Ref 522897ClinicalTrials.gov (NCT01034995) A Trial Evaluating the Efficacy and Tolerability of SSR125543 in Outpatients With Major Depressive Disorder. U.S. National Institutes of Health.
Ref 523144ClinicalTrials.gov (NCT01187511) Effects of Corticotropin-Releasing Hormone Receptor 1 (CRH1) Antagonism on Stress-Induced Craving in Alcoholic Women With High Anxiety. U.S. National Institutes of Health.
Ref 527521Strategies for producing faster acting antidepressants. Drug Discov Today. 2005 Apr 15;10(8):578-85.
Ref 536580Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2.
Ref 540427(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. (Ligand id: 3489).
Ref 540436(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. (Ligand id: 3498).
Ref 540437(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. (Ligand id: 3499).
Ref 546326Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007484)
Ref 546625Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009248)
Ref 546853Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010650)
Ref 546984Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011782)
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 527873Bioorg 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.
Ref 529324J 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.
Ref 529622Bioorg Med Chem Lett. 2008 Aug 15;18(16):4486-90. Epub 2008 Jul 18.2-Arylpyrimidines: novel CRF-1 receptor antagonists.
Ref 530071J 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.
Ref 530226J 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.
Ref 532181Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism. Drug Alcohol Depend. 2013 Mar 1;128(3):175-86.
Ref 534796Bioorg Med Chem Lett. 1998 Aug 18;8(16):2067-70.Pyrazolo[1,5-a]pyrimidine CRF-1 receptor antagonists.
Ref 534886Chronic 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.
Ref 536307A review of drug options in age-related macular degeneration therapy and potential new agents. Expert Opin Pharmacother. 2006 Dec;7(17):2355-68.
Ref 536580Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. Epub 2008 Jan 2.
Ref 549823Pharma & Vaccines. Product Development Pipeline. April 29 2009.
Ref 550543CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
Ref 550963Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).

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