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CRF1 receptor

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Target not currently curated in GtoImmuPdb

Target id: 212

Nomenclature: CRF1 receptor

Family: Corticotropin-releasing factor receptors

Gene and Protein Information Click here for help
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 444 17q21.31 CRHR1 corticotropin releasing hormone receptor 1 6,50
Mouse 7 415 11 67.77 cM Crhr1 corticotropin releasing hormone receptor 1 50
Rat 7 415 10q32.1 Crhr1 corticotropin releasing hormone receptor 1 4,33
Previous and Unofficial Names Click here for help
CRFR1 | CRF-R | CRHR | CRH-R1 | CRF-R1alpha | CRF 1 receptor | CRF-RA
Database Links Click here for help
Specialist databases
GPCRDB crfr1_human (Hs), crfr1_mouse (Mm), crfr1_rat (Rn)
Other databases
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Extracellular domain of CRFR1in complex with CRF its natural ligand
PDB Id:  3EHU
Ligand:  corticotrophin-releasing hormone   This ligand is endogenous
Resolution:  1.96Å
Species:  Human
References:  35
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex with the antagonist CP-376395
PDB Id:  4K5Y
Ligand:  CP 376,395
Resolution:  2.98Å
Species:  Human
References:  23
Natural/Endogenous Ligands Click here for help
corticotrophin-releasing hormone {Sp: Human, Mouse, Rat}
urocortin 2 {Sp: Human}
urocortin 1 {Sp: Human} , urocortin 1 {Sp: Mouse, Rat}

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]urocortin 1 (mouse, rat) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 10.0 pKd 34
pKd 10.0 [34]
[125I]sauvagine (frog) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.8 – 10.0 pKd 11,14
pKd 9.8 – 10.0 [11,14]
[125I]CRF (ovine) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.5 pKd 6,10
pKd 9.5 [6,10]
[125I]Tyr0-CRF (human, rat, mouse) Peptide Ligand is labelled Ligand is radioactive Hs Full agonist 9.3 pKd 14
pKd 9.3 [14]
urocortin 1 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.6 – 9.5 pKd 11,14-15
pKd 8.6 – 9.5 [11,14-15]
urocortin 1 {Sp: Mouse, Rat} Peptide Click here for species-specific activity table Hs Full agonist 8.3 – 9.8 pKd 14-15,24,34,49
pKd 8.3 – 9.8 [14-15,24,34,49]
urotensin 1 (fish) Peptide Click here for species-specific activity table Hs Full agonist 7.8 – 9.4 pKd 14,49
pKd 7.8 – 9.4 [14,49]
corticotrophin-releasing hormone {Sp: Human, Mouse, Rat} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 7.1 – 9.0 pKd 6,10,14-15,32,49
pKd 7.1 – 9.0 [6,10,14-15,32,49]
corticotropin-releasing factor {Sp: Sheep} Peptide Click here for species-specific activity table Hs Full agonist 7.2 – 8.9 pKd 10-11,14,32
pKd 7.2 – 8.9 [10-11,14,32]
sauvagine Peptide Click here for species-specific activity table Hs Full agonist 6.7 – 9.2 pKd 10-11,14-15,34,49
pKd 6.7 – 9.2 [10-11,14-15,34,49]
urocortin 2 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 5.3 – 5.4 pKd 11
pKd 5.3 – 5.4 [11]
Agonist Comments
See Table 1 in the 'introduction' for sequences similarities of the common endogenous ligands.

Ovine CRF is more selective than human/rat CRF.
For urocortin 1 no species differences have been identified thus far.

Agonist potencies:
CRF (ovine) (9.0-9.5); CRF (human) (9.0-9.5); urocortin 1 (human) (9.2-10); sauvagine (frog) (9.2-10)(units: pEC50).
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]astressin Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.2 – 9.3 pKd 11,14
pKd 9.2 – 9.3 [11,14]
astressin Peptide Click here for species-specific activity table Hs Antagonist 7.7 – 8.8 pKd 14,32,34
pKd 7.7 – 8.8 [14,32,34]
α-helical CRF Peptide Hs Antagonist 7.3 – 7.8 pKd 34
pKd 7.3 – 7.8 [34]
astressin Peptide Click here for species-specific activity table Hs Antagonist 8.7 pKi 39
pKi 8.7 (Ki 2x10-9 M) [39]
SSR125543A Small molecule or natural product Hs Antagonist 8.7 pKi 16
pKi 8.7 [16]
antalarmin Small molecule or natural product Hs Antagonist 8.3 – 9.0 pKi 51
pKi 8.3 – 9.0 (Ki 5.01x10-9 – 1x10-9 M) [51]
DMP696 Small molecule or natural product Hs Antagonist 8.3 – 9.0 pKi 19
pKi 8.3 – 9.0 (Ki 5.01x10-9 – 1x10-9 M) [19]
NBI27914 Small molecule or natural product Hs Antagonist 8.3 – 9.0 pKi 5
pKi 8.3 – 9.0 (Ki 5x10-9 – 1x10-9 M) [5]
R121919 Small molecule or natural product Hs Antagonist 8.3 – 9.0 pKi 53
pKi 8.3 – 9.0 (Ki 5x10-9 – 1x10-9 M) [53]
NBI-35965 Small molecule or natural product Rn Antagonist 8.4 pKi 27
pKi 8.4 (Ki 4x10-9 M) [27]
NBI-34041 Small molecule or natural product Hs Antagonist 8.3 pKi 17
pKi 8.3 (Ki 5.1x10-9 M) [17]
verucerfont Small molecule or natural product Hs Antagonist 8.2 pKi 46
pKi 8.2 (Ki 6.31x10-9 M) [46]
CP-316,311 Small molecule or natural product Hs Antagonist 8.1 pKi 7
pKi 8.1 (Ki 8.5x10-9 M) [7]
Description: Antagonism of CRF-stimulated adenylate cyclase activity by the CRF1 receptor endogenously expressed in human IMR32 cells.
CP 154,526 Small molecule or natural product Rn Antagonist 9.3 – 10.4 pIC50 26
pIC50 9.3 – 10.4 (IC50 5.1x10-10 – 3.9x10-11 M) [26]
astressin Peptide Click here for species-specific activity table Hs Antagonist 9.1 pIC50 38
pIC50 9.1 (IC50 7.2x10-10 M) [38]
ONO-2333MS Small molecule or natural product Hs Antagonist 8.4 pIC50 40
pIC50 8.4 (IC50 4x10-9 M) [40]
CP 376,395 Small molecule or natural product Ligand has a PDB structure Rn Antagonist 8.3 pIC50 8
pIC50 8.3 (IC50 5.01x10-9 M) [8]
CP-316,311 Small molecule or natural product Rn Antagonist 8.2 pIC50 7
pIC50 8.2 (IC50 6.8x10-9 M) [7]
Description: In vitro binding to rat cortex.
pexacerfont Small molecule or natural product Rn Antagonist 6.9 pIC50 28
pIC50 6.9 (IC50 1.29x10-7 M) [28]
Description: Antagonism of CRF-mediated ACTH production in rat pituitary cells.
CRA1000 Small molecule or natural product Hs Antagonist 6.4 – 7.1 pIC50 3
pIC50 6.4 – 7.1 (IC50 3.98x10-7 – 7.94x10-8 M) [3]
pexacerfont Small molecule or natural product Hs Antagonist 6.5 pIC50 28
pIC50 6.5 (IC50 3.4x10-7 M) [28]
Description: Displacement of ovine [125-I]-CRF from human CRF1 receptor expressed in CHO cell membranes.
astressin 2B Peptide Click here for species-specific activity table Hs Antagonist <6.3 pIC50 38
pIC50 <6.3 (IC50 >5x10-7 M) [38]
View species-specific antagonist tables
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043306 positive regulation of mast cell degranulation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043306 positive regulation of mast cell degranulation IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0043306 positive regulation of mast cell degranulation IEA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  1,4,6,10,29,31-33,36,50,52
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  So far only conclusively shown for recombinant expression systems
References:  11,52
Tissue Distribution Click here for help
Widespread distribution of CRF1 mRNA in neocortex, limbic structures, cerebellum and pituitary. In the periphery only limited expression in adrenal gland, testis, ovaries and skin.
Species:  Rat
Technique:  immunocytochemistry.
References:  30,37
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
COS-7 cells transiently transfected with CRF1.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  increase of intracellular cAMP.
References:  33
HEK 293 cells stably transfected with CRF1.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase of intracellular cAMP.
References:  10,14,32
Physiological Functions Click here for help
Agonist-induced CRF1 receptor activation increases anxiety-like behavior in open field, elevated plus maze, and many other tests measuring forms of defensive behavior, Moreover, CRF1 receptor activation is both necessary and sufficient to define the behavioral stress response.
Species:  Human
Tissue:  Brain
References:  2,9,20-21,41-42,45,47
Activation of CRF1 receptors on anterior pituitary corticotropes by direct agonist administration or acute stress exposure rapidly increases ACTH secretion. Increases in circulating levels of ACTH then activate ACTH receptors in the adrenal cortex leading to release of glucorcorticoids.
Species:  Human
Tissue:  Pituitary
References:  12-13,18,42,47-48
CRF1 receptor activation mediates stress-induced stimulation of colonic secretory and motor function.
Species:  Rat
Tissue:  Colon
References:  44
Physiological Consequences of Altering Gene Expression Click here for help
Less anxiety-like behavior in CRF1-deficient animals. ACTH and CORT levels reduced under stress conditions in these animals.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  42,47
Less anxiety-like behavior in socially stressed rats after infusion of CRF1 antisense oligonucleotides when compared to control groups.
Species:  Rat
Tissue: 
Technique:  Antisense oligonucleotide.
References:  22,25
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1tm1Wrst
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0008289 abnormal adrenal medulla morphology PMID: 9620773 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0001362 abnormal anxiety-related response PMID: 11756502 
Crhr1tm1Klee|Crhr2tm1Klee Crhr1tm1Klee/Crhr1tm1Klee,Crhr2tm1Klee/Crhr2tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MGI:894312  MP:0001362 abnormal anxiety-related response PMID: 11756502 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0005449 abnormal food intake PMID: 10919255 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0003953 abnormal hormone level PMID: 9655498 
Crhr1tm1Klee|Crhr2tm1Klee Crhr1tm1Klee/Crhr1tm1Klee,Crhr2tm1Klee/Crhr2tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MGI:894312  MP:0003953 abnormal hormone level PMID: 11756502 
Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1tm1Wrst
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0003953 abnormal hormone level PMID: 9620773 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0001449 abnormal learning/ memory PMID: 10448190 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0001175 abnormal lung morphology PMID: 9655498 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0002270 abnormal respiratory alveoli morphology PMID: 9655498 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0008294 abnormal zona fasciculata morphology PMID: 9655498 
Crhr1tm1Klee|Crhr2tm1Klee Crhr1tm1Klee/Crhr1tm1Klee,Crhr2tm1Klee/Crhr2tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MGI:894312  MP:0008294 abnormal zona fasciculata morphology PMID: 11756502 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0000640 adrenal gland hypoplasia PMID: 11756502  9655498 
Crhr1tm1Klee|Crhr2tm1Klee Crhr1tm1Klee/Crhr1tm1Klee,Crhr2tm1Klee/Crhr2tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MGI:894312  MP:0000640 adrenal gland hypoplasia PMID: 11756502 
Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1tm1Wrst
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0001987 alcohol preference PMID: 11988580 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0001364 decreased anxiety-related response PMID: 10448190  9655498 
Crhr1tm2Wrst|Tg(Camk2a-cre)159Kln Crhr1tm2Wrst/Crhr1tm2Wrst,Tg(Camk2a-cre)159Kln/0
involves: 129S2/SvPas * C57BL/6
MGI:2176751  MGI:88498  MP:0001364 decreased anxiety-related response PMID: 12973355 
Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1tm1Wrst
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0001364 decreased anxiety-related response PMID: 9620773 
Crhr1+|Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1+
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0001364 decreased anxiety-related response PMID: 9620773 
Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1tm1Wrst
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0009776 decreased behavioral withdrawal response PMID: 9620773 
Crhr1+|Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1+
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0009776 decreased behavioral withdrawal response PMID: 9620773 
Crhr1tm2Wrst|Tg(Camk2a-cre)159Kln Crhr1tm2Wrst/Crhr1tm2Wrst,Tg(Camk2a-cre)159Kln/0
involves: 129S2/SvPas * C57BL/6
MGI:2176751  MGI:88498  MP:0001399 hyperactivity PMID: 12973355 
Crhr1tm2Wrst|Tg(Camk2a-cre)159Kln Crhr1tm2Wrst/Crhr1tm2Wrst,Tg(Camk2a-cre)159Kln/0
involves: 129S2/SvPas * C57BL/6
MGI:2176751  MGI:88498  MP:0001748 increased circulating adrenocorticotropin level PMID: 12973355 
Crhr1tm2Wrst|Tg(Camk2a-cre)159Kln Crhr1tm2Wrst/Crhr1tm2Wrst,Tg(Camk2a-cre)159Kln/0
involves: 129S2/SvPas * C57BL/6
MGI:2176751  MGI:88498  MP:0001745 increased circulating corticosterone level PMID: 12973355 
Crhr1tm2Wrst Crhr1tm2Wrst/Crhr1tm2Wrst
involves: 129S2/SvPas * C57BL/6
MGI:88498  MP:0002169 no abnormal phenotype detected PMID: 12973355 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0002083 premature death PMID: 9655498 
Crhr1tm1Wrst Crhr1tm1Wrst/Crhr1tm1Wrst
either: (involves: 129P2/OlaHsd * 129P/Ola) or (involves: 129P2/OlaHsd * CD-1)
MGI:88498  MP:0002083 premature death PMID: 9620773 
Crhr1tm1Klee Crhr1tm1Klee/Crhr1tm1Klee
involves: 129S4/SvJae * C57BL/6
MGI:88498  MP:0001954 respiratory distress PMID: 9655498 
General Comments
A similar tissue distribution of CRF1 mRNA exists in rhesus monkey as in rodents.
Technique: Receptor autoradiography and immunocytochemistry.
Reference: [43]

References

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1. Arai M, Assil IQ, Abou-Samra AB. (2001) Characterization of three corticotropin-releasing factor receptors in catfish: a novel third receptor is predominantly expressed in pituitary and urophysis. Endocrinology, 142 (1): 446-54. [PMID:11145609]

2. Bale TL, Vale WW. (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol, 44: 525-57. [PMID:14744257]

3. Chaki S, Okuyama S, Nakazato A, Kumagai T, Okubo T, Ikeda Y, Oshida Y, Hamajima Y, Tomisawa K. (1999) In vitro pharmacological profile of nonpeptide CRF1 receptor antagonists, CRA1000 and CRA1001. Eur J Pharmacol, 371 (2-3): 205-11. [PMID:10357258]

4. Chang CP, Pearse 2nd RV, O'Connell S, Rosenfeld MG. (1993) Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Neuron, 11 (6): 1187-95. [PMID:8274282]

5. Chen C, Dagnino R, De Souza EB, Grigoriadis DE, Huang CQ, Kim KI, Liu Z, Moran T, Webb TR, Whitten JP et al.. (1996) Design and synthesis of a series of non-peptide high-affinity human corticotropin-releasing factor1 receptor antagonists. J Med Chem, 39 (22): 4358-60. [PMID:8893829]

6. Chen R, Lewis KA, Perrin MH, Vale WW. (1993) Expression cloning of a human corticotropin-releasing-factor receptor. Proc Natl Acad Sci USA, 90 (19): 8967-71. [PMID:7692441]

7. Chen YL, Braselton J, Forman J, Gallaschun RJ, Mansbach R, Schmidt AW, Seeger TF, Sprouse JS, Tingley 3rd FD, Winston E et al.. (2008) Synthesis and SAR of 2-aryloxy-4-alkoxy-pyridines as potent orally active corticotropin-releasing factor 1 receptor antagonists. J Med Chem, 51 (5): 1377-84. [PMID:18260619]

8. Chen YL, Obach RS, Braselton J, Corman ML, Forman J, Freeman J, Gallaschun RJ, Mansbach R, Schmidt AW, Sprouse JS et al.. (2008) 2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists. J Med Chem, 51 (5): 1385-92. [PMID:18288792]

9. Coste SC, Kesterson RA, Heldwein KA, Stevens SL, Heard AD, Hollis JH, Murray SE, Hill JK, Pantely GA, Hohimer AR et al.. (2000) Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Genet, 24 (4): 403-9. [PMID:10742107]

10. Dautzenberg FM, Dietrich K, Palchaudhuri MR, Spiess J. (1997) Identification of two corticotropin-releasing factor receptors from Xenopus laevis with high ligand selectivity: unusual pharmacology of the type 1 receptor. J Neurochem, 69 (4): 1640-9. [PMID:9326293]

11. Dautzenberg FM, Gutknecht E, Van der Linden I, Olivares-Reyes JA, Dürrenberger F, Hauger RL. (2004) Cell type specific calcium signaling by corticotropin-releasing factor type 1 (CRF1) and 2a (CRF2(a)) receptors: Gq coupling in human embryonic kidney 293 but not SK-N-MC neuroblastoma cells. Biochem Pharmacol, 68: 1833-1844. [PMID:15450949]

12. Dautzenberg FM, Hauger RL. (2002) The CRF peptide family and their receptors: yet more partners discovered. Trends Pharmacol Sci, 23: 71-77. [PMID:11830263]

13. Dautzenberg FM, Kilpatrick GJ, Hauger RL, Moreau J. (2001) Molecular biology of the CRH receptors-- in the mood. Peptides, 22 (5): 753-60. [PMID:11337088]

14. Dautzenberg FM, Py-Lang G, Higelin J, Fischer C, Wright MB, Huber G. (2001) Different binding modes of amphibian and human corticotropin-releasing factor type 1 and type 2 receptors: evidence for evolutionary differences. J Pharmacol Exp Ther, 296 (1): 113-20. [PMID:11123370]

15. Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW. (1996) Cloning and characterization of human urocortin. Endocrinology, 137 (5): 2167-70. [PMID:8612563]

16. Gully D, Geslin M, Serva L, Fontaine E, Roger P, Lair C, Darre V, Marcy C, Rouby PE, Simiand J et al.. (2002) 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization. J Pharmacol Exp Ther, 301 (1): 322-32. [PMID:11907190]

17. Guo Z, Tellew JE, Gross RS, Dyck B, Grey J, Haddach M, Kiankarimi M, Lanier M, Li BF, Luo Z et al.. (2005) Design and synthesis of tricyclic imidazo[4,5-b]pyridin-2-ones as corticotropin-releasing factor-1 antagonists. J Med Chem, 48 (16): 5104-7. [PMID:16078829]

18. Hauger RL, Dautzenberg FM. (1999) Regulation of the stress response by corticotropin-releasing factor receptors. In Physiology and Medicine. Edited by Conn PM, Freedman ME (Humana Press Inc.) 261-286. [ISBN:0896037250]

19. He L, Gilligan PJ, Zaczek R, Fitzgerald LW, McElroy J, Shen HS, Saye JA, Kalin NH, Shelton S, Christ D et al.. (2000) 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2, 4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: a potent, orally bioavailable CRF(1) receptor antagonist. J Med Chem, 43 (3): 449-56. [PMID:10669572]

20. Heinrichs SC, De Souza EB. (1999) Corticotropin-releasing factor antagonists, binding-protein and receptors: implications for central nervous system disorders. Baillieres Best Pract Res Clin Endocrinol Metab, 13 (4): 541-54. [PMID:10903813]

21. Heinrichs SC, Koob GF. (2004) Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther, 311 (2): 427-40. [PMID:15297468]

22. Heinrichs SC, Lapsansky J, Lovenberg TW, De Souza EB, Chalmers DT. (1997) Corticotropin-releasing factor CRF1, but not CRF2, receptors mediate anxiogenic-like behavior. Regul Pept, 71 (1): 15-21. [PMID:9299637]

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