Cibinetide Improves Experimental Colitis By Inhibiting Innate Immune Cell

Erythropoietin (EPO) is a type I cytokine with dual functions. In the classical endocrine function, erythropoietin produced by kidney plays a key regulator of erythropoietin by inhibiting the apoptosis of erythroid progenitor cells and stimulating differentiation. In addition, erythropoietin produced locally mediates erythropoietin activity in non hematopoietic cells and tissues. Therefore, EPO has been used as a tissue protective and anti apoptotic cytokine in animal models of ischemia, ischemia-reperfusion injury or mechanical injury. In addition, studies have shown that erythropoietin can improve the disease activity of experimental arthritis, encephalomyelitis and colitis in mice, indicating that erythropoietin has anti-inflammatory and tissue protective effects in autoimmune diseases.

Cibinetide (also known as ara290 or phbsp) is a synthetic oligopeptide designed to selectively activate irr24. Cibinetide interacts with the external hydrophilic domain of EPOR / CD131 complex, which shows beneficial effects in animal models of myocardial infarction, dilated cardiomyopathy, experimental ischemic stroke, peripheral nerve injury and wound healing. In addition, randomized placebo-controlled trials have demonstrated its safety and efficacy in human subjects with sarcoidosis or peripheral neuropathy secondary to mellite diabetes. Cibinetide can improve the symptoms of patients with sarcoidosis associated small nerve fiber loss and increase the abundance of corneal small nerve fibers.

Cibinetide lacks erythropoiesis because it does not activate EpoR homodimer. Accordingly, Hb levels did not change after repeated use of cibinetide. Therefore, cibinet is not associated with unintended side effects, such as secondary thromboembolism caused by full-length recombinant erythropoietin.

The aim of this study was to investigate the therapeutic effect of cibinetide in experimental DSS colitis model, and to explore the possible mechanism of its immunomodulatory effect. The results showed that cibineti had extensive and effective anti-inflammatory effects on bone marrow cells.

Therefore, inhibition of NF - κ B activation is a direct and promising intervention for the treatment of different types of colitis. Cibinetide may interfere with the autocrine and paracrine stimulation of cytokines produced by macrophages and other immune cells in the inflammatory microenvironment. Therefore, the addition of sibinet to existing drugs may help to reduce the dose and thus limit the side effects associated with the current treatment regimen. In addition, cibinetide is especially valuable for patients with resistance to conventional treatment or allergic symptoms. Another benefit is the lack of EPO induced erythropoietin side effects, such as blood hyperviscosity and increased risk of thromboembolic events.

Cibinetide has been shown to have profound anti-inflammatory and disease modifying activities in DSS induced colitis, but there is no evidence of unexpected erythropoiesis. The results of the study are encouraging to launch a randomized controlled trial to study the therapeutic potential of sibinet for human IBD.

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