CRFR1
Cortagine is a highly specific and selective agonist for the CRF1 receptor. Unlike other CRF family peptides such as oCRF, cortagine does not bind significantly to CRF2 receptors. It selectively binds and activates CRF1, which primarily couples to the Gs alpha subunit. CRF1 activation affects neuronal activity, anxiety, depression, and autonomic functions.

In transfected HEK-293 cells, cortagine suppresses mCRF2β (EC50=16 nM) and rCRF1 (EC50=0.18 nM)[1].

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In vitro, cortagine's specificity for CRF1 has been demonstrated in autoradiographic experiments by its selective binding to CRF1 in mouse brain sections. It shows potent, dose-dependent activation of CRF1. Cortagine does not activate CRF2, making it a valuable tool for dissecting the distinct roles of CRF1 versus CRF2 signaling.

In nine-week-old male C57BL/6J mice, cortagine (30, 100, 300 ng; icv) significantly reduces the percentage of time in the open arms and the number of open arm entries during the elevated plus-maze (EPM) test[1].

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In vivo, administration of cortagine via intracerebroventricular (i.c.v.) injection in male C57BL/6J mice enhances anxiety-like behaviors in the elevated plus maze (EPM) and open-field test at lower doses compared to oCRF. It also shows antidepressant-like effects in the forced swim test (FST). Chronic i.c.v. administration (10 ng/day for 5 days) alters the expression of hippocampal and prefrontal cortex genes implicated in anxiety and aversive memory formation.

Cortagine is typically used to assess CRF1 activation in autoradiographic binding experiments. Mouse brain sections (coronal, 20 microM thickness) are incubated with 0.05 nM [125I]Tyr-ovine CRF in the presence of increasing concentrations of unlabeled Cortagine (0-1000 nM). Non-specific binding is defined with 1 microM oCRF. After 90 minutes at room temperature, sections are washed, dried, and exposed to phosphorimaging plates to generate autoradiograms. Specific binding is quantitated. For cell-based cAMP assays, cells expressing CRF1 are used (see cell assay).For cell-based assays, HEK293 cells stably expressing human CRF1 are seeded in 96-well plates (50,000 cells/well). Cells are incubated with 500 microM IBMX for 10 minutes, then treated with varying concentrations of Cortagine (0-1000 nM) for 30 minutes at 37degC. cAMP accumulation is measured using an HTRF cAMP kit. The EC50 for cAMP activation is calculated. Cortagine shows pEC50 values characteristic of potent CRF1 agonists (typically in the low nM range).For animal studies, male C57BL/6J mice (8-12 weeks old) are used. For i.c.v. administration, mice are anesthetized and stereotaxically implanted with a guide cannula into the lateral ventricle. After recovery, Cortagine is dissolved in artificial cerebrospinal fluid (aCSF) and administered i.c.v. (e.g., 10-100 ng per mouse in 2-5 microL). Behavioral testing begins 15-30 minutes post-injection. The elevated plus maze (EPM) test is conducted for 5 minutes; anxiety-like behavior is measured as percent open arm time and open arm entries. The forced swim test (FST) measures antidepressant-like effect as decreased immobility time. For chronic studies, 10 ng/day is administered for 5 days; brain tissue is collected for gene expression analysis.Cortagine is a 29- or 30-amino acid peptide (sequence derived from CRF but modified for selectivity). It is typically supplied as a lyophilized TFA salt and stored at -20degC. It is soluble in water (1 mg/mL) and DMSO. For i.c.v. administration, it is diluted in aCSF or saline. As a peptide, it has a short half-life in vivo (minutes). The compound is stable for years when stored lyophilized at -20degC.Cortagine is a research-grade peptide not for human use. At research doses (e.g., 10-100 ng i.c.v. in mice), it is generally well-tolerated with no acute toxicity. Standard safety precautions for handling peptides (avoid inhalation, skin contact) should be followed. It is for laboratory research use only. Purity is typically ≥95-98% by HPLC.Cortagine is a specific CRF1 agonist used to study the role of CRF1 in anxiety, depression, and the stress response. It is a valuable tool for dissecting the functions of CRF1 versus CRF2 receptors, as it exhibits no significant binding to CRF2 at relevant concentrations. It is not approved for clinical use.

[1]. Cortagine, a Specific Agonist of Corticotropin-Releasing Factor Receptor Subtype 1, Is Anxiogenic and Antidepressive in the Mouse Model. Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9468-73.

C192H323N55O63S

4442.06

White to off-white solid powder

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO :~50 mg/mL (~11.26 mM)

Solubility in Formulation 1: 2.5 mg/mL (0.56 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (0.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)