Peptides > ARA-290


ARA-290 is a modified form of erythropoietin known for its ability to reduce inflammatory pathways through paracrine signaling and innate repair receptors. Studies have demonstrated that ARA-290 can have positive effects, such as lowering HbA1c levels, enhancing cholesterol profiles, alleviating neuropathic pain, and promoting wound healing.

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1. ARA-290 Introduction


2. ARA-290 Structure


3. Research on ARA-290

ARA-290 Introduction

ARA-290, a small peptide derived from erythropoietin’s beta helix domain, extends beyond its known role in stimulating red blood cell production. Erythropoietin, produced in the kidney, has been recognized for its capacity to encourage blood vessel growth, support cell survival, impact blood pressure, and offer neuroprotective benefits in diabetic neuropathy. ARA-290 replicates EPO’s neuroprotective and pain-relieving qualities without triggering red blood cell production. Phase II trials have been successfully completed, and preparations are underway for Phase III trials, exploring its potential in diabetes and the autoimmune condition sarcoidosis. Currently, ARA-290 is particularly promising for its ability to manage neuropathic pain, but ongoing research is investigating its potential as a wound repair stimulant in chronic diabetes, an immune-modulating medication, and a potential treatment for systemic lupus erythematosus (lupus or SLE).


Molecular Formula: C51H84N16O21
Molecular Weight: 1257.3 g/mol
PubChem CID: 91810664
CAS No: 1208243-50-8
Synonyms: cibinetide, PH-BSP


Blood Vessel Health

Retinal ischemia, a leading cause of blindness in developed countries, arises from various diseases. Protecting retinal epithelial cells from damage and promoting their regeneration could significantly reduce the disease’s impact. Research in mice demonstrates that ARA-290 has the potential to shield endothelial colony-forming cells (ECFCs) from inflammation, thereby prolonging their survival and assisting in the repair and reconstruction of blood vessels.

Additional mouse studies indicate that ARA-290 enhances ECFCs’ proliferation, migration, and lifespan throughout the vasculature. It also appears to enhance ECFCs’ homing ability, enabling them to target areas of the vasculature requiring repair. There is optimism that this function could not only enhance the effectiveness of naturally occurring ECFCs but also improve the capability of transplanted ECFCs to repair blood vessels and restore circulation to ischemic tissue. If successful in ECFC transplants, ARA-290 may open up new avenues in medical therapy, enabling the successful transplantation of functional cells for tissue repair, hormone production, protein synthesis, and more.

Reducing Inflammatory Cytokines

Research conducted in mice has shown that ARA-290 can enhance the survival of transplanted islet cells by inhibiting the activation of macrophages. For years, the transplantation of healthy insulin-producing islet cells has been a sought-after goal in diabetes treatment. Unlike external insulin, islet cells offer more natural blood sugar control, reducing complications often associated with diabetes, even when well-managed. Unfortunately, transplanted islet cells have had limited longevity, leading to a decline in the procedure’s use. However, the development of ARA-290 may change this outlook. Mouse studies have demonstrated that the peptide’s ability to suppress inflammatory cytokines like IL-6, IL-12, and TNF-alpha significantly extends the lifespan of transplanted islet cells.

ARA-290’s capacity to shield against typical inflammatory responses seems to occur by binding to the tissue-protective receptor (TPR), enhancing tissue protection, and aiding immune system regulation. Erythropoietin (EPO) also binds to the TPR but has cardiovascular and hematopoietic side effects that limit its use in many situations. Peptides like ARA-290, by binding to the TPR without promoting some of EPO’s other effects, help reduce cell death and lower levels of harmful inflammatory cytokines. This results in tissue protection, enhanced tissue regeneration, reduced morbidity and mortality, rapid wound healing, decreased scar formation, and swift post-injury functional recovery.

Tissue Protection

The tissue-protective receptor (TPR) is found on various immune cells, including macrophages, dendritic cells, mast cells, and lymphocytes, notably T-cells. Emerging evidence indicates that ARA-290 and similar peptides can bind to this TPR on immune cells, directly influencing their function.

In the case of macrophages, ARA-290’s stimulation of the TPR leads to a significant reduction in the release of proinflammatory cytokines like TNF-alpha and IL-6. Interestingly, while this dampening of the immune response may decrease pathogen clearance in certain situations, it also lowers disease severity and hinders the establishment of long-term disease processes. Research further suggests that TPR activation curbs the pathway of macrophage chemokine secretion, reducing the infiltration of inflammatory cytokines while enhancing the recruitment of tissue-resident macrophages to injury sites. The outcome appears to be improved tissue healing with fewer inflammatory side effects.

Additionally, studies indicate that ARA-290 may modify antigen presentation by dendritic cells, thus influencing adaptive immunity, which plays a role in long-term resistance against previously encountered pathogens. While this may initially seem concerning, it’s important to note that adaptive immunity primarily drives organ and tissue rejection following transplantation. The ability to modulate this process can help reduce graft rejection in various transplant scenarios, including kidney, heart, bone marrow, and experimental transplants.

ARA-290 holds promise in various medical applications. One particularly promising avenue is in the treatment of colitis, a condition that can result from infection or chronic autoimmune diseases like Crohn’s disease and ulcerative colitis. Current treatments for autoimmune colitis often involve injectable medications with numerous side effects. The use of more targeted immune modulators like ARA-290 could provide relief for individuals suffering from inflammatory bowel disease.

Another potential application of ARA-290’s immune modulatory effects is in treating systemic lupus erythematosus (SLE). Research in mice indicates that ARA-290 administration reduces levels of autoantibodies, such as ANA and anti-dsDNA, which serve as markers for SLE diagnosis and indicators of disease severity. Furthermore, ARA-290 diminishes kidney damage, a common source of morbidity and mortality in SLE. These findings suggest that ARA-290 may offer a highly targeted treatment option for SLE.

Pain Perception

The immune system has long been recognized as a contributor to pain perception, especially in neuropathic pain conditions like diabetic neuropathy. Managing neuropathic pain has proven to be a significant challenge, but recent research highlights the potential of targeting the innate repair receptor (IRR) to reduce inflammation and alleviate this type of pain. ARA-290 is known to interact with the IRR, but emerging research suggests that it can also inhibit the activity of the TRPV1 channel, often referred to as the capsaicin receptor. This channel is responsible for the perception of heat and the burning pain frequently associated with neuropathic diseases. ARA-290’s ability to influence this receptor could make it a valuable option for treating pain linked to conditions such as diabetes, multiple sclerosis, chemotherapy, and amputation.

Small nerve fiber loss, a consequence of certain autoimmune disorders like sarcoidosis and diabetes, leads to a condition known as small fiber neuropathy. This condition occurs when the small sensory fibers responsible for temperature and pain sensations in the skin deteriorate. Symptoms can vary in intensity, ranging from a pins-and-needles sensation to feelings of discomfort akin to having sand in a shoe or a wrinkle in a sock. Pain is typically intermittent but can be severe, occurring multiple times throughout the day. In more severe cases, the pain becomes persistent and is often described as a burning sensation. Research conducted in individuals affected by small fiber nerve loss demonstrates that ARA-290 treatment increases the number of small nerve fibers and significantly reduces pain. These findings suggest that ARA-290 may offer an effective treatment for nerve damage associated with conditions like sarcoidosis, diabetes, thyroid dysfunction, celiac disease, HIV, and more.

Orphan Drug

In 2016, Araim Pharmaceuticals received orphan drug status from the FDA for the investigation of daily cibinetide in the treatment of painful sarcoid neuropathy. One year later, Dr. Michael Brines, Chief Science Officer, and a team of researchers published a paper highlighting the positive effects of ARA-290 in addressing peripheral nerve pain and small nerve fiber pain.

Dr. Brines and his colleagues have disclosed that ARA-290, also known as cibinetide, is moving towards phase 3 clinical trials as a potential treatment for neuropathy. This peptide holds promise in addressing the needs of the approximately 87 million Americans living with nerve damage and its associated health challenges. Additionally, there are indications that ARA-290 may have a role in expediting impaired wound healing in diabetic mice, suggesting its potential to mitigate the risk of amputations and chronic ulcers that many individuals with diabetes face later in life.


While ARA-290 has garnered significant attention for its innovative approach to managing neuropathic pain, it also holds promise for its immune-regulating properties, its capacity to promote wound healing, and its potential for protecting blood vessels during ischemic events. The most advanced area of research revolves around ARA-290’s ability to modulate neuropathic pain. The peptide is currently undergoing phase II and III clinical trials for diabetic neuropathy and sarcoid neuropathy treatment, respectively. Additionally, there is growing interest in utilizing the peptide to treat conditions like systemic lupus erythematosus and pain syndromes associated with multiple sclerosis, HIV, celiac disease, and more. ARA-290 is also gaining attention as a potential disease-modifying agent in the context of inflammatory bowel disease.

ARA-290 has demonstrated minimal side effects, excellent subcutaneous bioavailability in mice, and is available for research purposes at Peptide Sciences. It is important to note that ARA-290 is intended solely for educational and scientific research and is not meant for human consumption. Purchases of ARA-290 should only be made by licensed researchers.

Article Author

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.


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