ARA-290

Research Overview

ARA-290 serves as a valuable research tool for investigating tissue protection and innate repair mechanisms in laboratory settings. This synthetic 11-amino acid peptide was rationally designed to retain the tissue-protective properties of erythropoietin (EPO) while eliminating erythropoietic activity. Research applications have expanded to encompass investigations of neuroprotection, inflammatory modulation, metabolic regulation, and cellular protection across multiple organ systems.

The peptide’s designation reflects its development as a targeted therapeutic candidate (ARA-290 development nomenclature) designed to activate innate repair pathways. Laboratory studies investigate ARA-290’s effects on inflammatory cytokine modulation, oxidative stress reduction, cellular survival pathways, and tissue protection mechanisms against various forms of injury. Research protocols examine these effects in cell culture systems, isolated tissue preparations, and preclinical animal models.

ARA-290 research demonstrates the peptide’s selective activity through the innate repair receptor without affecting erythropoiesis. This separation of tissue-protective effects from hematological activity represents a significant advantage in research applications. Studies have documented ARA-290’s ability to reduce inflammatory mediators, improve mitochondrial function, enhance cellular energy metabolism, and protect tissues from ischemic, inflammatory, and metabolic injury.

Molecular Characteristics

Complete Specifications:

• Peptide Type: Synthetic tissue-protective peptide
• Molecular Weight: ~1,000 Da
• Amino Acid Sequence: 11 amino acid derivative
• Design: Non-erythropoietic EPO receptor agonist
• Peptide Classification: Innate repair receptor agonist
• Appearance: White to off-white lyophilized powder
• Solubility: Water, bacteriostatic water, phosphate buffered saline

The peptide’s 11-amino acid structure was specifically engineered to interact with the innate repair receptor complex formed by erythropoietin receptor (EPOR) and CD131 (common beta chain). This selective receptor engagement activates tissue-protective signaling cascades including JAK2/STAT3, PI3K/AKT, and MAPK pathways while avoiding the STAT5 pathway responsible for erythropoiesis. The sequence represents a minimal active fragment optimized for tissue protection with reduced molecular size compared to full-length EPO.

Pharmacokinetic Profile in Research Models

ARA-290 pharmacokinetic characterization in preclinical research reveals important properties for experimental design:

Absorption and Distribution:

• Multiple administration routes investigated: IV, SC, IP
• Rapid absorption from subcutaneous administration sites
• Systemic distribution with tissue penetration
• Blood-brain barrier penetration observed in some models

Metabolism and Elimination:

• Plasma half-life: Shorter than full-length EPO (minutes to hours depending on model)
• Renal clearance as primary elimination pathway
• Biological effects observed beyond plasma detection period
• Tissue retention may contribute to sustained activity

These pharmacokinetic characteristics inform research protocol design, particularly regarding dosing frequency and timing in experimental models. The relatively short plasma half-life requires consideration of dosing schedules to maintain tissue-protective effects in longer-term studies.

Research Applications

Neuroprotection and Neurological Research

ARA-290 serves as a research tool for investigating neuroprotective mechanisms. Laboratory studies examine the peptide’s effects on:

• Peripheral Neuropathy Models: Investigation of protective effects in diabetic neuropathy, chemotherapy-induced neuropathy, and other peripheral nerve injury models
• Neuroinflammation Studies: Analysis of central and peripheral neuroinflammatory pathway modulation
• Neuronal Survival Research: Examination of neuronal protection against oxidative stress, excitotoxicity, and metabolic stress
• Axonal Function Studies: Investigation of axonal transport, nerve conduction, and structural integrity maintenance
• Glial Cell Modulation: Research on microglial and astrocyte activation states and inflammatory responses

Research protocols typically employ neuronal cell cultures, dorsal root ganglion preparations, and animal models of neuropathy to characterize ARA-290’s neuroprotective mechanisms.

Metabolic and Diabetes Research

Substantial research focuses on metabolic regulation and diabetes-related applications:

• Insulin Sensitivity Studies: Investigation of insulin receptor signaling and glucose metabolism regulation
• Pancreatic Beta Cell Protection: Research on beta cell survival, insulin secretion, and protection against cytokine-induced damage
• Diabetic Complication Models: Studies examining protection against diabetic nephropathy, retinopathy, and cardiovascular complications
• Metabolic Inflammation Research: Analysis of inflammatory pathway modulation in metabolic tissues
• Mitochondrial Function Studies: Investigation of mitochondrial biogenesis, oxidative phosphorylation, and energy metabolism

Research in this area investigates ARA-290’s effects on glucose homeostasis, insulin signaling pathways, and protection of metabolic tissues in various experimental models.

Inflammatory Modulation Research

Laboratory studies investigate ARA-290’s anti-inflammatory mechanisms:

• Cytokine Modulation Studies: Research on TNF-α, IL-6, IL-1β, and other inflammatory mediator expression
• Immune Cell Function: Investigation of macrophage polarization, T-cell responses, and innate immune regulation
• Inflammatory Disease Models: Studies in arthritis, colitis, and other inflammatory disease models
• Acute Inflammation Research: Examination of protective effects in sepsis, ischemia-reperfusion, and acute injury models
• Resolution Pathway Analysis: Investigation of pro-resolving mechanisms and return to homeostasis

Experimental models include LPS-induced inflammation, cytokine challenge protocols, and various inflammatory disease models with assessment of inflammatory markers and tissue outcomes.

Cardiovascular Research Applications

Research applications extend to cardiovascular system investigation:

• Cardiac Protection Studies: Examination of cardioprotective mechanisms in ischemia-reperfusion and infarction models
• Endothelial Function Research: Investigation of vascular endothelial protection and nitric oxide pathways
• Vascular Inflammation Studies: Research on atherosclerosis models and vascular inflammatory responses
• Heart Failure Models: Analysis of cardiac remodeling, contractile function, and metabolic adaptations
• Microcirculation Research: Studies on capillary density, tissue perfusion, and microvascular function

Laboratory protocols investigate ARA-290’s effects on cardiomyocyte survival, endothelial cell function, and vascular protection in various cardiovascular injury models.

Renal and Kidney Research

Emerging research areas include renal protection investigation:

• Acute Kidney Injury Models: Research on ischemic and nephrotoxic kidney injury protection
• Diabetic Nephropathy Studies: Investigation of glomerular and tubular protection in diabetes models
• Chronic Kidney Disease Research: Studies examining progression modulation and fibrosis reduction
• Renal Inflammation Studies: Analysis of kidney inflammatory responses and immune cell infiltration
• Tubular Function Research: Investigation of tubular cell protection and transport function maintenance

Research in this area examines ARA-290’s effects on renal cell survival, inflammatory pathways, and functional outcomes in kidney injury models.

Laboratory Handling and Storage Protocols

Lyophilized Powder Storage:

• Store at -20°C to -80°C in original sealed vial
• Protect from light exposure and moisture
• Desiccated storage environment required
• Stability data available for 12+ months at -20°C

Reconstitution Guidelines:

• Reconstitute with sterile water, bacteriostatic water (0.9% benzyl alcohol), or appropriate buffer
• Add solvent slowly down vial side to minimize foaming
• Gentle swirling motion recommended (avoid vigorous shaking)
• Allow complete dissolution before use (typically 1-2 minutes)
• Final pH should be 7.0-8.0 for optimal stability

Reconstituted Solution Storage:

• Short-term storage: 4°C for up to 7 days
• Long-term storage: -20°C in aliquots to avoid freeze-thaw cycles
• Single-use aliquots recommended to maintain peptide integrity
• Avoid repeated freeze-thaw cycles (maximum 2-3 cycles)

Stability Considerations:
ARA-290 demonstrates typical peptide stability characteristics as a lyophilized powder under proper storage conditions. Reconstituted solutions should be aliquoted for long-term storage to prevent degradation from repeated freeze-thaw cycles.

Quality Assurance and Analytical Testing

Each ARA-290 batch undergoes comprehensive analytical characterization:

Purity Analysis:

• High-Performance Liquid Chromatography (HPLC): ≥98% purity
• Analytical method: Reversed-phase HPLC with UV detection at 214-220nm
• Multiple peak integration to ensure accurate purity determination

Structural Verification:

• Electrospray Ionization Mass Spectrometry (ESI-MS): Confirms molecular weight ~1,000 Da
• Amino acid analysis: Verifies sequence composition
• Peptide content determination: Quantifies actual peptide content by weight

Contaminant Testing:

• Bacterial endotoxin: <5 EU/mg (LAL method)
• Heavy metals: Below detection limits per USP standards
• Residual solvents: TFA and acetonitrile within acceptable limits
• Water content: Karl Fischer titration (<8%)

Documentation:

• Certificate of Analysis (COA) provided with each batch
• Third-party analytical verification available upon request
• Stability data documented for recommended storage conditions
• Batch-specific QC results traceable by lot number

Research Considerations

Experimental Design Factors:

Researchers should consider several factors when designing ARA-290 experiments:

1. Concentration Selection: Determine appropriate concentrations based on research objectives and experimental model. Published research reports concentrations ranging from nanomolar to micromolar depending on application and model system.

2. Temporal Considerations: ARA-290’s relatively short plasma half-life requires attention to dosing schedules. Effects on inflammatory markers and tissue protection may persist beyond plasma detection.

3. Route Considerations: Subcutaneous and intraperitoneal routes are commonly used in animal studies. Route selection should align with research questions and model requirements.

4. Model Selection: Choose appropriate cell culture systems, ex vivo preparations, or animal models based on specific research questions regarding tissue protection or inflammation.

5. Control Groups: Include appropriate vehicle controls, positive controls (where applicable), and comparative compounds such as EPO for mechanistic studies.

Mechanism Investigation:

ARA-290’s mechanisms of action involve selective innate repair receptor activation. Multiple pathways have been investigated including:

• JAK2/STAT3 signaling pathway activation
• PI3K/AKT survival pathway engagement
• MAPK pathway modulation
• NF-κB inflammatory pathway inhibition
• Oxidative stress response pathway activation

The peptide’s selective receptor engagement provides opportunities to investigate tissue-protective pathways independent of erythropoietic effects.

Compliance and Safety Information

Regulatory Status:
ARA-290 is provided as a research chemical for in-vitro laboratory studies and preclinical research only. This product has not been approved by the FDA for human therapeutic use, dietary supplementation, or medical applications.

Intended Use:

• In-vitro cell culture studies
• In-vivo preclinical research in approved animal models
• Laboratory investigation of biological mechanisms
• Academic and institutional research applications

NOT Intended For:

• Human consumption or administration
• Therapeutic treatment or diagnosis
• Dietary supplementation
• Veterinary therapeutic applications without appropriate oversight

Safety Protocols:
Researchers should follow standard laboratory safety practices when handling ARA-290:

• Use appropriate personal protective equipment (lab coat, gloves, safety glasses)
• Handle in well-ventilated areas or fume hood
• Follow institutional biosafety guidelines
• Dispose of waste according to local regulations for biological/chemical waste
• Consult material safety data sheet (MSDS) for additional safety information

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