ARA-290 16mg


Size: 16mg
Contents: ARA-290 (16mg)
Form: Lyophilized powder
Purity: >99%
SKU: P-ARA290-16
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ARA-290 Peptide Basics

ARA-290 peptide is a 11 amino acid chain derived from the beta domain of protein erythropoietin, a part of the erythropoietin known to possess properties such as tissue protection and repair (1).

This peptide was initially thought to have a sole function of upregulating blood cells in the body; however, persistent research led to further biological uses of this peptide – including neuroprotection and pain relieving effects. Clinical studies are ongoing to establish the safe and effective peptide profile, mainly to treat nerve pain, tissue and wound repairs.

Historical Background

While not much evidence is found outlining the discovery of the ARA-290 peptide, it is known that it was the discovery of the Innate Repair Receptor (IRR) that led to finding this peptide molecule (2).

The current status of the peptide is that it has completed the initial clinical trial phase I and II, and is undergoing phase III studies, particularly for its use in the treatment of Sarcoidosis – an orphan neuropathy disease, discussed later in this post (3).

ARA-290 Peptide – the Versatile “Pain Relief” Medication

One of the well known facts is that the human body is composed of about 38 trillion cells. Human blood cells are mainly divided into three categories known as red blood cells, white blood cells and platelets. Red blood cells, just like the other two types, are vital for human existence. The body protein that regulates the synthesis and maintenance of these red blood cells is called erythropoietin, or simply EPO (1).

The primary function of EPO is to stimulate body tissues to produce red blood cells. While the mechanism is not fully understood, EPO mainly optimizes the oxygen levels in the body – when the levels are low, more EPO is produced; when the levels are optimal, lesser EPO is produced (1).

Researchers have isolated a small peptide molecule from the EPO protein, called Cibinetide, or simply ARA-290 peptide. Initially thought to help regulate blood cell levels in the body, ARA-290 has shown versatile properties expanding its use in various other biological aspects. This article captures all you need to know about this new peptide.

Mechanism of Action

Innate Repair Receptor Pathway

As per the scientific evidence available (4), once the tissue undergoes an injury, a tissue protective receptor (TPR) pathway is activated. This TPR receptor mainly consists of a beta receptor unit (CD131) along with a subunit from the EPO receptor, jointly called the innate repair receptor.

The ARA-290 peptide molecule binds to this innate repair receptor and helps attenuate nerve pain, as well allodynia led pain (i.e., pain caused by an otherwise non-pain inducing stimulus such as sunburn) and pain caused by inflammation (2).

It is strongly believed that ARA-290 peptide acts mainly via this IRR mediated pathway.

Inhibition of TRPV1 Channel

Transient Receptor Potential (TRP) channels mainly detect the pain stimuli in the human body, including several thermal, chemical, and mechanical stimuli. In the presence of such a causative agent, one of the TRP channels, namely TRPV1, gets stimulated. Upon activation, it stimulates the ejection of neuropeptides, which then generate action potential in the nervous systems. This action potential is what is often referred to as “pain” (5).

A 2016 study (6) showed that ARA-290 peptide acts as an antagonist to this TRPV1 channel, which implies that the peptide inhibits the TRPV1 actions and thereby no neuropeptides are released leading to pain.

This discovery has led to several more studies depicting that the peptide can be highly useful in pain management.

Biological Uses of ARA-290 Peptide

ARA-290, or the Cibinetide peptide, have shown various advantageous biological effects including:

  • Regulating the levels of red blood cells
  • Maintaining the health of the blood vessels
  • Decreasing levels of inflammatory cells, thereby reducing inflammation led pain
  • Demonstrating tissue protective properties
  • Demonstrating immunomodulatory properties
  • Reduce the levels of pain

Research and Clinical Studies

Retinal Ischemia

Recent study (7) has shown that ARA-290 has the potential to protect the endothelial blood vessels and thereby combat retinal ischemia.

Retinal ischemia, mainly an end-point in several diseases threatening one’s vision, is a common cause towards blindness. One of the ways to overcome this ailment is to restore endothelial colonial forming (ECF) cells in the retinal cells.

Experimental mice models, induced with retinal ischemia, underwent the ECF cells transplantation for the purpose of this study. To determine the efficacy of the peptide, the transplantation in some mice occurred in the presence of ARA-290 while the rest was in peptide absence.

After the study, it was noticed that the peptide reduced the inflammatory expression of interleukin cells in the retina. Thus, following the transplantation, there was minimal inflammation and faster recovery in the presence of the peptide. This fact demonstrated that ARA-290 peptide could be a potent adjunct in ECF transplant therapy to restore the damaged retinal cells.

Studies Related to Tissue Protection

Protection Against Inflammatory Cytokine Cells (During Transplantation)

Erythropoietin cells are known to possess anti-inflammatory and cell protective properties. This study (8) was conducted to determine whether the erythropoietin analogue, ARA-290 peptide, also possessed similar properties.

Pancreatic islet cells are used to regulate the levels of blood sugar in the body. One of the potent ways to counter excessive diabetes is to transplant the damaged pancreatic islet cells with healthy ones. However, due to cellular damage and inflammatory reaction, this transplantation, thus far, had not proved to be beneficial.

In this study (8), experimental mice were used, which were treated with transplantation surgery for 180+ pancreatic islet cells. The mice were then administered with 120ug/kg body weight of ARA-290 peptide via intraperitoneal route right before the surgery and at 0, 6 and 24 hours after surgery. After 12 hours of treatment, the liver samples from the mice were collected and analyzed.

Peptide treated cells showed minimal damage of the islets. It was understood that the peptide protected the islet cells from cytokines and subsequent apoptosis. Consequently, ARA-290 peptide protected the pancreatic cells from cytokines, thereby proving itself to be a potent agent in improving the pancreatic cells’ transplant.

Overall Tissue Protection

Based on the research (9) conducted, it has become common knowledge that the ARA-290 peptide binds with the tissue protective receptors (TPR), which in turn helps to maintain the optimal health of the tissues protecting it against harmful inflammatory cells and subsequent cellular death. This in turn also helps to regulate the immune system.

The main advantage of ARA-290 peptide over the endogenous erythropoietin cells is that while both bind with TPR receptor cells, the peptide does not cause harmful cardiovascular and blood cells related side effects (9).

This feature of the peptide helps in improving tissue regeneration and thereby reducing tissue morbidity, promoting better wound recovery and healing, and decreasing formation of scars in the body.

Studies Exhibiting Immunomodulatory Properties

Via the TPR Pathway

The TPR pathway, once stimulated, is expressed on various immunological cells including macrophages.
When ARA-290 peptide binds with the TPR receptor cells, it restricts the release of certain inflammatory cells such as interleukin IL-6. Owing to this reduced secretion, it leads to reduced severity of the disease and prevents long term consequences of the ailments (9).

Via Alteration of the Adaptive Immunity

Adaptive immunity is something the body develops over time due to increased exposure towards any antigen.

Research (10) has shown that ARA-290 peptide may potentially alter the presentation of the antigen by the dendritic cells in the body and thereby alter the adaptive immunity. While this may seem like a “negative” effect, it is especially useful in the case of transplantation surgery. Owing to its ability to “fine tune” the antigens, the immune cells will not reject the transplanted organ, leading to minimal side effects.

Autoimmune Disorders Studies

Studies have shown that ARA-290 peptide may have potential therapeutic effects in treating autoimmune disorders including Systemic Lupus Erythematosus (SLE).

Severe liver ailments such Crohn’s disease, also an autoimmune ailment, may lead to ulcerative colitis (i.e., inflammation of colon). While there are several injectables used to combat colitis, they all lead to severe long term side effects.

A study (11) was conducted on mice suffering from colitis, which were administered with placebo and ARA-290 peptide. While the placebo treated mice showed no effects, the mice treated with ARA-290 peptide showed improved results including enhanced tissue quality, optimal weight gain and better prognosis. This was primarily due to the ability of the peptide to bind with the IRR receptor cells that exhibited anti-inflammatory properties, leading to reduced disease progression and reduced mortality in mice.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder which causes skin rashes, joint problems and sometimes, even kidney failure. Research (12) has shown that ARA-290 peptide administration leads to suppression of autoantibodies, primarily the ANA antibodies. These antibodies serve as SLE markers, and their levels indicate the severity of the disorder – where higher levels indicate more severity.

In addition, ARA-290 peptide also inhibited kidney damage which often leads to increased SLE associated fatality rate. These results suggest that the peptide may potentially be used in humans to treat, or at the least manage, SLE ailment.

Studies Associated with Sarcoidosis

Sarcoidosis is characterized by abnormal accumulation of the inflammatory cells causing the formation of lumps in the skin and/or lungs, leading to rashes and cough. Linked to Sarcoidosis is also small nerve fiber loss and damage (SNFLD) which leads to dysfunctioning of vital bodily organs, impacting the quality of life (2).

An initial clinical trial (2) was conducted on patients suffering from sarcoidosis where the effects of ARA-290 peptide were monitored after 3 back-to-back doses were administered intravenously over the course of one week. After the study, 50% improvement was seen in all patients with no safety concerns reported.

A follow up trial (2) was conducted in patients suffering from sarcoidosis with mild SNFLD symptoms. These patients underwent ARA-290 peptide administration via intravenous route 3 times a week for four weeks. After the study, the patients showed a significant improvement and well tolerance towards the peptide.

The most recent study (2) involved 38 patients (of the mean age of 50 years) suffering from sarcoidosis and associated SNFLD for almost 8 years. Patients were administered with 4mg ARA-290 peptide via subcutaneous route and the study lasted for 16 weeks, including the patient follow up. Once the study was completed, it was noted that there was a positive prognosis of the treatment with improvements seen in all the patients. While there were moderate side effects reported (discussed later in this article), all these reported adverse events were spontaneously resolved, with no reported long term side effects.

Side Effects Associated with ARA-290

The ARA-290 peptide is well tolerated by the human body, with no reported long term adverse events.

Some known side effects that may be associated with long term ARA-290 peptide use are (2):

  • May cause pain or temporary irritation at the site of administration
  • Diarrhea
  • Dizziness
  • Irritability, agitation
  • Weight loss (rare)

ARA-290 as Orphan Drug

In 2014, US FDA provided “fast track designation” to the ARA-290 peptide molecule. The US FDA mainly assigns this designation to those medications that have demonstrated significant potential to treat an orphan disease, a disease that so far has no approved treatment available (3).

The peptide has since been classified as an orphan drug by the US FDA and the European Regulatory authorities (3) based on the promising outcomes of the first clinical trials showing the peptide may be potentially used in the treatment of sarcoidosis and improvement in sensory functions.


ARA-290 peptide, also known as Cibinetide, is a 11 amino acid peptide isolated from the beta domain of endogenous protein erythropoietin. Known as the analogue of erythropoietin, this peptide has proven to be more beneficial as it demonstrates similar effects as the protein without causing any major adverse events.

The peptide exerts its properties by binding with the innate repair receptor (primary pathway) and inhibiting the TRPV1 cycle, both of which lead to reduced pain sensations and subsequent pain associated effects.

Research so far has demonstrated significant results indicating that the peptide may potentially be used to treat autoimmune ailments, act as adjuncts in transplant surgeries, and help combat tissue and wound injuries. Successful clinical Phase I and II trials of ARA-290 peptide in battling sarcoidosis have led the peptide to be designated as an ‘orphan drug’ to treat similar sensory defects.

Research and subsequent clinical trials continue till date to fully explore the potencies of the peptide and help establish the ARA-290 peptide molecule as a potent therapeutic agent to combat various human ailments.


1. What is Erythropoietin? Home Health Network.

2. Dahan, A., Dunne, A., Swartjes, M., Proto, P. L., Heij, L., Vogels, O., van Velzen, M., Sarton, E., Niesters, M., Tannemaat, M. R., Cerami, A., & Brines, M. (2013). ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density. Molecular medicine (Cambridge, Mass.), 19(1), 334–345.

3. Designation to ARA 290 for the Treatment of Sarcoidosis-associated Small Fiber Neuropathy.

4. Brines M, Cerami A. The receptor that tames the innate immune response. Mol Med. 2012 May 9;18(1):486-96.

5. Jara-Oseguera, A., Simon, S. A., & Rosenbaum, T. (2008). TRPV1: on the road to pain relief. Current molecular pharmacology, 1(3), 255–269.

6. Zhang W, Yu G, Zhang M. ARA 290 relieves pathophysiological pain by targeting TRPV1 channel: Integration between immune system and nociception. Peptides. 2016 Feb;76:73-9.

7. O’Leary OE, Canning P, Reid E, Bertelli PM, McKeown S, Brines M, Cerami A, Du X, Xu H, Chen M, Dutton L, Brazil DP, Medina RJ, Stitt AW. The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic. Exp Eye Res. 2019 May;182:144-155.

8. Watanabe M, Lundgren T, Saito Y, Cerami A, Brines M, Östenson CG, Kumagai-Braesch M. A Nonhematopoietic Erythropoietin Analogue, ARA 290, Inhibits Macrophage Activation and Prevents Damage to Transplanted Islets. Transplantation. 2016 Mar;100(3):554-62.

9. Peng, B., Kong, G., Yang, C. et al. Erythropoietin and its derivatives: from tissue protection to immune regulation. Cell Death Dis 11, 79 (2020).

10. Yan L, Zhang H, Gao S, Zhu G, Zhu Q, Gu Y, Shao F. EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway. Transplant Proc. 2018 Jun;50(5):1575-1582.

11. Nairz, M., Haschka, D., Dichtl, S. et al. Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis. Sci Rep 7, 13012 (2017).

12. Bo Huang et al, Non-erythropoietic erythropoietin-derived peptide protects mice from systemic lupus erythematosus, published 23 March 2018.


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