Urocortin-2
Also known as: SRP, Stresscopin-related peptide, Ucn2, Urocortin II
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Summary
Urocortin‑2 (Ucn‑2) is a 38‑amino‑acid peptide of the corticotropin‑releasing factor family. It signals chiefly through the type‑2 corticotropin‑releasing hormone receptor (CRHR2) and is being explored for metabolic and cardiovascular uses, such as preserving lean mass during weight loss and protecting the heart from failure‑related injury. The compound is not approved for any therapeutic indication and is currently studied only in research settings, typically administered by injection.
Mechanism of Action
Ucn‑2 binds with high affinity to CRHR2, a G‑protein‑coupled receptor found on cardiomyocytes, vascular endothelial cells and skeletal‑muscle tissue. Activation stimulates adenylate cyclase, raising cAMP and activating protein kinase A, and also engages phospholipase‑C pathways that trigger PKCε, Src tyrosine kinase and the ERK1/2 cascade. These downstream signals enhance cardiac contractility, promote vasodilation via cAMP‑ and cGMP‑dependent mechanisms, inhibit apoptosis, protect mitochondria, and may stimulate energy‑expenditure pathways that support lean‑mass preservation.
What the Research Shows
Pre‑clinical studies repeatedly show that Ucn‑2 improves coronary blood flow, augments cardiac output and limits ischemia‑reperfusion injury through CRHR2‑mediated signaling. Animal models of chronic heart failure report better survival and cardiac performance after chronic Ucn‑2 administration. Early‑phase clinical trials in patients with stable chronic heart failure have demonstrated hemodynamic benefits when added to optimal therapy. Observational work in acute heart‑failure patients linked higher circulating Ucn‑2 to markers of volume overload and pulmonary hypertension, suggesting a potential biomarker role. A 2022 obesity review highlighted Ucn‑2 as a candidate for preserving lean mass during weight loss, though no human trials in this area have been reported. Evidence for bone‑related effects remains speculative, limited to review‑level discussion.
Reported Benefits
Ucn‑2 shows promise for preserving lean mass during aggressive weight‑loss regimens, a benefit noted in expert reviews. In cardiovascular research, the peptide consistently improves cardiac contractility, promotes vasodilation, and reduces ischemia‑reperfusion injury in animal models, with early human trials indicating enhanced hemodynamics in chronic heart‑failure patients. Elevated serum levels correlate with volume‑overload signs in acute heart failure, suggesting diagnostic or prognostic utility. Overall, the evidence points to potential metabolic and cardioprotective advantages, though most data are pre‑clinical or from small early‑phase studies.
Limitations of the Evidence
Ucn‑2 has not received regulatory approval for any indication; its therapeutic use remains experimental. Human data are limited to a few early‑phase trials and observational studies, many of which involve small sample sizes and short follow‑up. The metabolic benefits described in obesity reviews are theoretical and have not been tested in clinical trials. Long‑term safety, optimal dosing, and comparative effectiveness versus existing therapies are still unknown, creating substantial gaps before clinical adoption.
Safety Considerations
Safety information is sparse in the published literature. Pre‑clinical work reports no major toxicities, but vasodilatory actions raise the possibility of hypotension, especially with intravenous dosing. Early human trials in heart‑failure patients did not report serious adverse events, yet comprehensive safety profiling has not been completed. Potential immunogenicity, peptide degradation and off‑target hormonal effects remain theoretical concerns that require systematic evaluation in larger, controlled studies.
How It Is Administered
Ucn‑2 is studied as an injectable peptide, typically delivered by intravenous or subcutaneous injection. Formulations are aqueous solutions suitable for sterile administration. Dosing regimens in research vary widely, and no standardized clinical protocol exists.
Routes of Administration
Goals & Uses
- Heart failure treatmentCardiovascularModerate
- Stress response modulationNeuropsychiatricLow
- Metabolic syndrome improvementMetabolicLow
- Muscle preservation / anabolic effectsMusculoskeletalLow
- Vasodilation and afterload reductionCardiovascularModerate
- Appetite suppression / weight regulationMetabolicLow
Contraindications
- HypovolemiaCardiovascularHigh
- Obstructive cardiomyopathyCardiovascularModerate
- Hypersensitivity to Ucn2 or CRF-family peptidesAllergy/ImmunologyHigh
- Known hypersensitivity to urocortin‑2 or formulation excipientsAllergicHigh
- Severe hypotensionCardiovascularHigh
Adverse Effects
- HeadacheNeurologicCommonPain in the head or upper neck
- HypotensionCardiovascularCommonLow blood pressure
- FlushingVascularCommonWarmth and redness of the skin
- TachycardiaCardiovascularUncommonAbnormally fast heart rate
- NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
Drug Interactions
- Antihypertensive agentsModerate
- CRF1R antagonistsLow
- Beta‑blockersModerate
- Vasodilators (e.g., nitrates, hydralazine)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Renal impairmentOrgan ImpairmentRelative
- Pediatric patientsAgeRelative
- Elderly patientsAgeRelative
- Pregnant womenReproductiveRelative
Regulatory Status
- European UnionInvestigationalClinical trial authorization only; not marketed.
- United StatesInvestigationalInvestigational New Drug (IND) status; no FDA approval.
- United KingdomInvestigationalNo marketing authorization; used under clinical trial regulations.
Not approved for clinical use in any jurisdiction; studied in early‑phase clinical trials for chronic heart failure and metabolic disorders.
Evidence & Sources
- Journal ArticleModerateChristoffersen BØ, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModeratePopov SV, et al.2021-01-01T00:00:00.000000Z
- Journal ArticleModerateMonteiro-Pinto C, et al.2019-01-01T00:00:00.000000Z
- Journal ArticleModeratePintalhao M, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateAdão R, et al.2015-01-01T00:00:00.000000Z
- Journal ArticleModerateIsmail OM, El-Omar OM, Said UN2023-01-01T00:00:00.000000Z
Frequently Asked Questions
What condition is Ucn‑2 currently approved to treat?
Ucn‑2 is not approved for any medical condition. It is still an investigational peptide used only in research studies.
How does Ucn‑2 differ from other heart‑failure drugs?
Unlike conventional agents that mainly block neuro‑hormonal pathways, Ucn‑2 activates CRHR2, leading to direct increases in cardiac contractility, vasodilation and cellular protection, offering a distinct mechanism that is still under investigation.
Could Ucn‑2 be used to help with weight loss?
Reviews suggest Ucn‑2 might help preserve lean muscle during calorie restriction, but no human trials have tested this use yet, so its role in weight‑loss therapy remains hypothetical.
What are the main safety concerns for Ucn‑2?
The principal theoretical risk is excessive vasodilation causing low blood pressure. Overall safety data are limited, and larger trials are needed to define adverse‑event profiles.
How is Ucn‑2 administered in studies?
Researchers administer Ucn‑2 by intravenous or subcutaneous injection of a sterile peptide solution; oral or other routes have not been described.
What is Urocortin-2?
Urocortin‑2 (Ucn‑2) is a 38‑amino‑acid peptide of the corticotropin‑releasing factor family. It signals chiefly through the type‑2 corticotropin‑releasing hormone receptor (CRHR2) and is being explored for metabolic and cardiovascular uses, such as preserving lean mass during weight loss and protecting the heart from failure‑related injury. The compound is not approved for any therapeutic indication and is currently studied only in research settings, typically administered by injection.
What is Urocortin-2 used for?
Urocortin-2 is educationally associated with: Heart failure treatment, Stress response modulation, Metabolic syndrome improvement, Muscle preservation / anabolic effects, Vasodilation and afterload reduction, Appetite suppression / weight regulation. Educational only — not medical advice.
How is Urocortin-2 administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of Urocortin-2?
Reported adverse effects include: Headache, Hypotension, Flushing, Tachycardia, Nausea. This list is not exhaustive — consult a qualified clinician.
Who should avoid Urocortin-2?
Recorded contraindications: Hypovolemia, Obstructive cardiomyopathy, Hypersensitivity to Ucn2 or CRF-family peptides, Known hypersensitivity to urocortin‑2 or formulation excipients, Severe hypotension. Consult a qualified clinician before use.