CRFR1

CRFR1 (corticotropin-releasing factor receptor 1, CRHR1) is a class B G protein-coupled receptor that binds corticotropin-releasing hormone (CRH) and urocortin, serving as a central regulator of endocrine, autonomic, behavioral, and immune responses to stress^[1]^[2]. Mechanistically, CRFR1 predominantly couples to G_s proteins, activates adenylyl cyclase, increases cAMP production, and engages downstream PKA, PKC, and MAPK signaling pathways that shape tissue-specific stress responses^[1]^[3]. Within the hypothalamic-pituitary-adrenal (HPA) axis, CRFR1 signaling in pituitary corticotrophs promotes ACTH release and coordinates neuroendocrine adaptation to stress exposure^[1]^[4]. In disease-relevant models, genetic deletion or pharmacological inhibition of CRFR1 reduces anxiety-like behavior and blunts stress reactivity, supporting its role in stress-related neuropsychiatric disorders^[1]^[4]^[5]. CRFR1 also regulates neuronal excitability, fear learning, memory-related processes, and GABAergic transmission in limbic circuits that are frequently disrupted during chronic stress and alcohol dependence^[1]^[5]^[6]. Compared with the related isoform CRFR2, CRFR1 displays broader forebrain and pituitary expression, higher functional involvement in stress initiation, and distinct ligand selectivity, whereas CRFR2 is more closely associated with stress recovery and peripheral regulation^[1]^[7]. For experimental applications, selective CRFR1 antagonists, including antalarmin, CP-154,526, and DMP-696, are widely used to investigate stress signaling, anxiety phenotypes, and HPA-axis dysregulation in preclinical models^[5]^[8].

References:

[1]. Hauger RL, et al. International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands. Pharmacol Rev. 2003 Mar;55(1):21-6.

[2]. Chen R, et al. Expression cloning of a human corticotropin-releasing-factor receptor. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8967-71.

[3]. Hillhouse EW, et al. The molecular mechanisms underlying the regulation of the biological activity of corticotropin-releasing hormone receptors: implications for physiology and pathophysiology. Endocr Rev. 2006 May;27(3):260-86.

[4]. Kiros M, et al. Trends in HIV-1 pretreatment drug resistance and HIV-1 variant dynamics among antiretroviral therapy-naive Ethiopians from 2003 to 2018: a pooled sequence analysis. Virol J. 2023 Oct 25;20(1):243. [Content Brief]

[5]. Koob GF, et al. Update on corticotropin-releasing factor pharmacotherapy for psychiatric disorders: a revisionist view. Neuropsychopharmacology. 2012 Jan;37(1):308-9.

[6]. Nie Z, et al. Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science. 2004 Mar 5;303(5663):1512-4.

[7]. Piao G, et al. Ion-Enhanced Conversion of CO₂ into Formate on Porous Dendritic Bismuth Electrodes with High Efficiency and Durability. ChemSusChem. 2020 Feb 21;13(4):698-706. [Content Brief]

[8]. Rabezanahary H, et al. Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Québec, Canada. Heliyon. 2024 May 21;10(10):e31026. [Content Brief]

CRFR1 Related Products (18):

By Type:	Pan (1) Selective (9)
By Effects:	Inhibitor (1) Agonists (4) Antagonists (12) Modulator (1)

Cat. No.	Product Name	Effect	Purity

HY-14127

R121919	Antagonist	99.66%
R121919 (NBI30775) is a potent and selective CRF1R antagonist with a K_i of 2 to 5 nM. R121919 has antidepressant and anxiolytic effects. R121919 alleviates defensive withdrawal in rats.

HY-P2847

Urocortin II, mouse	Agonist	99.94%
Urocortin II, mouse is a potent and selective endogenous peptide agonist of type-2 corticotropin-releasing factor (CRF2) receptor with K_i values of 0.66 nM and ﹥100 nM for CRFR2 and CRFR1, respectively. Urocortin II, mouse activates CRF2 receptors in a cAMP/PKA- and Ca²⁺/CaMKII-dependent manner.Urocortin II, mouse is expressed in discrete areas of the central nervous system, and activates central neurons involved in the processing of visceral sensory information, and in modulating autonomic outflow.

HY-P2287

Cortagine	Agonist	98.68%
Cortagine is a specific corticotropin-releasing factor receptor subtype 1 (CRF1) agonist with an EC₅₀ of 2.6 nM for rCRF1. Cortagine is an anxiolytic and antidepressive agent in the mouse model.

HY-14875

Verucerfont	Antagonist	99.93%
Verucerfont is a corticotropin-releasing factor receptor 1 (CRF1) antagonist with IC₅₀s of ~6.1, >1000 and >1000?nM for CRF1, CRF2, and CRF-BP, respectively.

HY-14130

CP 376395	Antagonist	99.59%
CP 376395 is a potent, selective, and brain-penetrable Corticotropin releasing factor 1 (CRF1) receptor antagonist.

HY-182645

CRF1 receptor antagonist-2	Antagonist
CRF1 receptor antagonist-2 is an orally active, blood-brain barrier permeable CRF1 receptor antagonist, with an IC₅₀ of 4 nM in CHO-K1 cell membranes and an IC₅₀ of 7 nM in rat brain cell membranes. CRF1 receptor antagonist-2 exerts anxiolytic effects in swim stress-loaded rats. CRF1 receptor antagonist-2 can be used in studies related to stress-induced anxiety.

HY-P1296

Urocortin, rat	Agonist	99.23%
Urocortin, rat (Urocortin (Rattus norvegicus)) is a neuropeptide and a potent endogenous CRFR agonist with K_is of 13 nM, 1.5 nM, and 0.97 nM for human CRF₁, rat CRF_2α and mouse CRF_2β, respectively.

HY-P1294A

α-Helical CRF(9-41) TFA	Modulator	99.91%
α-Helical CRF(9-41) TFA is a competitive CRF2 receptor antagonist with K_B of ~100 nM. α-Helical CRF(9-41) TFA is also a partial agonist of CRF1 receptor with an EC₅₀ of 140 nM.

HY-113603

Tildacerfont	Inhibitor	98.60%
Tildacerfont (SPR001; LY2371712) is an orally active, blood-brain barrier-penetrant selective corticotropin-releasing factor type 1 (CRF1) receptor antagonist. Tildacerfont selectively blocks CRF1 receptors, thereby inhibiting the release of pituitary adrenocorticotropic hormone (ACTH). Tildacerfont can be used in research related to congenital adrenal hyperplasia.

HY-103376

NBI-27914 hydrochloride	Antagonist
NBI-27914 (hydrochloride) is a selective Corticotropin-Releasing Factor 1 (CRF1) receptor antagonist with a K_i value of 1.7 nM.

HY-103378

NBI 35965 methanesulfonate	Antagonist
NBI 35965 methanesulfonate is a selective, orally active and brain-penetrant corticotropin-releasing factor receptor 1 (CRF1) antagonist with a K_i value of 4 nM and a pK_i value of 8.5. NBI 35965 methanesulfonate does not inhibit CRF2. NBI 35965 methanesulfonate reduces CRF or stress-induced adrenocorticotropic hormone (ACTH) production in vivo with pIC₅₀ values of 7.1 and 6.9, respectively. NBI 35965 methanesulfonate shows anxiolytic effects.

HY-115645

R121919 hydrochloride	Antagonist
R121919 (NBI30775) hydrochloride is a potent and selective CRF1R antagonist with a K_i of 2 to 5 nM. R121919 hydrochloride has antidepressant and anxiolytic effects. R121919 hydrochloride alleviates defensive withdrawal in rats.

HY-103379

CP 376395 hydrochloride	Antagonist
CP 376395 hydrochloride is a potent, selective, and brain-penetrable Corticotropin releasing factor 1 (CRF1) receptor antagonist.

HY-110056

NBI 35965 hydrochloride	Antagonist
NBI 35965 hydrochloride is a selective, orally active and brain-penetrant corticotropin-releasing factor receptor 1 (CRF1) antagonist with a K_i value of 4 nM and a pK_i value of 8.5. NBI 35965 hydrochloride does not inhibit CRF2. NBI 35965 hydrochloride reduces CRF or stress-induced adrenocorticotropic hormone (ACTH) production in vivo with pIC₅₀ values of 7.1 and 6.9, respectively. NBI 35965 hydrochloride shows anxiolytic effects.

HY-P3959

(Tyr0)-Urocortin, rat	Agonist
(Tyr0)-Urocortin, rat is a high-affinity agonist of corticotropin-releasing factor receptor type 1 (CRF-R1) and type 2 (CRF-R2). (Tyr0)-Urocortin, rat shows inhibitory binding constants (Ki) of 1-2 nM.

HY-14129

CP 316311	Antagonist
CP 316311 is a potent and selective CRF1 receptor antagonist with an IC₅₀ value of 6.8 nM.

HY-14128

NBI-34041	Antagonist
NBI-34041 (SB-723620) is a selective and orally active nonpeptide CRF1 receptor antagonist with an IC₅₀ of 58.9 nM and a K_i of 4.0 nM for human CRF1 receptor. NBI-34041 has no inhibitory effect on the CRF2 receptor. NBI-34041 can be used for depression and anxiety disorders research.

HY-162872

NBI-35965	Antagonist
NBI-35965 is an antagonist of corticotropin-releasing factor receptor 1 (CRF-R1). NBI-35965 can be used in nervous system related research.

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