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Cibinete, also known as ARA290 or pHBSP, is a well-designed synthetic oligopeptide that selectively activates IRR24. The interaction between the external hydrophilic domains of Sibeniet and EPOR/CD131 complex has shown beneficial effects in animal models of myocardial infarction, dilated cardiomyopathy, experimental ischemic stroke, peripheral nerve injury, and wound healing. Cibinete This compound improves the symptoms of patients with tuberculosis related small nerve fiber deficiency and increases the abundance of small nerve fibers in the cornea.
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Xibinai lacks erythropoietic activity because it does not activate EPOR homodimers. Therefore, after repeated use of the compound, there was no change in hemoglobin levels in the patient. Therefore, cibinatide is not associated with unexpected side effects.
It may help interfere with the autocrine and paracrine stimulation of cytokines by macrophages and other immune cells in the inflammatory microenvironment. Therefore, adding sibenitide to existing drugs may help reduce dosage, thereby limiting the toxic side effects associated with current treatment regimens. This substance is particularly valuable in patients who are resistant to conventional treatment or experience allergic symptoms.
| Density | 1.6±0.1 g/cm3 |
| Molecular Formula | C51H84N16O21 |
| Molecular Weight | 1257.307 |
| Exact Mass | 1256.599731 |
| LogP | -6.59 |
| Refractive index | 1.661 |
| Storage condition | -20°C |
Cibinetide function
Cibinetide is mainly used in the pharmaceutical field and has significant effects on neurological diseases and anti-inflammatory effects.
Cibinetide has the ability to improve symptoms and increase the abundance of corneal small nerve fibers in patients with tuberculosis-associated small nerve fiber
deficits.
Cibinetide has the ability to ameliorate symptoms and increase the abundance of corneal small nerve fibers in patients with nodular disease-associated small nerve fiber deficits.
Cibinetide showed a broad and potent anti-inflammatory effect on myeloid cells, which may help interfere with autocrine and paracrine stimulation of cytokine production by macrophages and other immune cells in the inflammatory microenvironment. This means that the addition of Cibinetide to existing treatment regimens may help to reduce the dose of medication required, thereby limiting the toxic side effects associated with current treatments.
Cibinetide has shown potential in the treatment and study of neurological disorders, particularly in improving small nerve fiber deficits and anti-inflammatory effects. However, further research and clinical trials are needed to validate its specific applications and effects.
Current Applications and Development Trends of Cibinetide
Cibinetide is currently mainly used in the fields of medicine and pharmaceutical intermediates, with specific applications in the following aspects:
Treating Neurological Disorders
This compound is mainly used in the pharmaceutical field in the market, especially as a pharmaceutical intermediate. Xibinapeptide, as an EPO like peptide, has specific biological activity that acts on erythropoietin/CD131 heteroreceptors, and has the potential to treat neurological diseases.
Cibinetide In Anti-inflammatory Effects
This compound has anti-inflammatory properties and may help reduce the side effects of current treatment regimens. Although it has shown some potential in the field of scientific research, it is not an approved drug for treating humans or animals. Therefore, its market application is still mainly focused on being used as a pharmaceutical intermediate or scientific research reagent. With the deepening of scientific research and the advancement of clinical trials, the application scope of this compound may be further expanded.
Cibinetide In Immune Regulation
This compound also has immunomodulatory effects. Some studies suggest that it may improve experimental colitis by inhibiting the function of innate immune cells. Specifically, it may help interfere with the autocrine and paracrine stimulation of cytokines by macrophages and other immune cells in the inflammatory microenvironment, thereby weakening the inflammatory response.
It is worth noting that the compound has achieved encouraging results in neurological diseases, but it is still in the research stage and has not yet been widely applied in clinical practice. Therefore, further clinical research is needed to verify the exact efficacy and safety of this compound in treating neurological diseases.
Translated with www.DeepL.com/Translator (free version).
What is the effect of this compound on different types of neurodegenerative diseases?
Alzheimer's Disease (AD)
There is no direct evidence to suggest that the compound has a direct impact on Alzheimer's disease. However, the common pathophysiological mechanisms of neurodegenerative diseases such as AD include abnormal aggregation of misfolded proteins and dysregulation of autophagosome lysosome pathways. As an EPO derivative, it may exert its effects by influencing these common pathological mechanisms.
Parkinson's Disease (PD)
Similarly, there is no direct evidence to suggest that the compound has an effect on Parkinson's disease. However, considering that one of the characteristics of Parkinson's disease is the loss of dopamine neurons, as well as factors such as oxidative stress, inflammatory response, and mitochondrial dysfunction, it may indirectly affect PD by regulating these factors.
Amyotrophic Lateral Sclerosis (ALS)
There is no direct evidence to suggest that the compound has therapeutic effects on ALS. The characteristic of ALS is the extensive degeneration of motor neurons, and as an EPO derivative, its impact on motor neurons is still unclear.
Multiple Sclerosis, MS
There is no direct evidence to suggest that the compound has an effect on MS. MS is a central nervous system demyelinating disease, and its mechanism of action may be related to its potential effects on neuroprotection and immune regulation.
How does this compound improve myocardial infarction in animal models?
The mechanism by which Cibinetide improves myocardial infarction in animal models mainly involves the following aspects:
- Anti inflammatory effect: As a synthetic oligopeptide, it can selectively activate IRR24 and interact with the external hydrophilic domain of EPOR/CD131 complex, exerting its anti-inflammatory and tissue protective effects. In animal models of myocardial infarction, it reduces inflammation by inhibiting the expression of pro-inflammatory cytokines, thereby alleviating myocardial injury.
- Promote macrophage polarization: After myocardial infarction, monocytes are recruited to the infarcted area and form macrophages. These macrophages, after clearing dead cells and matrix debris, transform into M2 macrophages and play a role in myocardial repair. This compound may have a protective effect on myocardial infarction repair by promoting macrophage polarization towards M2 type.
- Improving cardiac function: This compound has shown beneficial effects in animal models such as myocardial infarction and dilated cardiomyopathy, and can improve cardiac function. This may be related to its anti apoptotic, anti-inflammatory, and anti permeability effects, simulating the effects of endogenous EPO without the potential side effects of EPO, such as high blood viscosity and increased risk of thromboembolic events.
- Promoting angiogenesis: This compound may provide necessary nutrition and oxygen to the healing site by promoting angiogenesis after AMI, helping to establish collateral circulation, restore blood supply, reduce scar formation, and delay the deterioration of cardiac function. It is an effective method for treating AMI.
- The research results showed that the compound showed safety and effectiveness in human subjects with sarcoidosis or peripheral neuropathy secondary to Merlot diabetes. Specifically, it can improve the symptoms of small nerve fiber deficiency in patients with sarcoidosis and increase the abundance of corneal small nerve fibers. These research results indicate that the compound has certain potential in the treatment of sarcoidosis.
- However, it should be noted that due to the relatively complex etiology and pathological mechanism of sarcoidosis, and the possible differences in the condition and response of different patients, its treatment effect may also vary from person to person. In addition, there is currently relatively little research on the efficacy of this compound in treating sarcoidosis, and there may be some unknown risks and side effects.
What are the highlights of the clinical trial results of this compound?
The highlights of Cibinetide's clinical trial results are as follows:
- Safety: The compound showed good safety during a 12 week course of treatment. Among the patients participating in the study, no serious adverse events or reactions were observed, and no antibodies against it were detected.
- Patient reported improvement in outcomes: Although no average improvement was observed in primary and secondary outcomes such as best corrected visual acuity (BCVA), central retinal thickness (CRT), central retinal sensitivity, or tear production, improvement was observed in the comprehensive score of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).
- Individual patient improvement: Improvements in CRT, tear production, diabetes control, and albuminuria were observed in some participants. These improvements may be related to the potential therapeutic effects of the compound and warrant further investigation.
- Potential benefits of retinal function: Improvement in central retinal sensitivity has been observed in some non study eyes with mild edema, further indicating its potential benefits for retinal function in early disease.
- Improvement of tear production and corneal nerve fibers: This compound leads to an improvement in tear production, especially in patients with reduced basal tear formation. NEI VFQ-25 also showed improvement in eye pain, which may be a result of the beneficial effects of the compound on the cornea.
- Improvement in metabolic control: The compound has been observed to improve metabolic control in some subjects, which is consistent with preclinical studies showing increased insulin sensitivity and improved blood glucose control in rodent models.
- Improvement of renal function: all patients with abnormal ACR (albuminuria) at baseline showed improvement indicators at the 12th week, which was consistent with the preclinical data of its efficacy in the diabetes kidney injury related model.
Biological activity
Cibinetide (ARA290) possesses a variety of biological activities. The following is a detailed introduction from aspects such as cell proliferation and migration, apoptosis resistance, angiogenesis, blood glucose regulation, treatment of neurological diseases, and immune regulation:
Enhancing cell proliferation and migration: In vitro experiments have shown that it can enhance the proliferation and migration capabilities of endothelial colony-forming cells (ECFCs).
Enhance cell resistance to apoptosis: It can increase the resistance of ECFCs to H2O2-induced apoptosis and help protect cells from oxidative stress damage.
Improving angiogenesis: In vivo experiments have shown that a single injection can increase blood flow and capillary density in the hind limbs of mice and promote the homing of transplanted cells, which has a positive effect on angiogenesis.
Regulating blood glucose levels: Without affecting the body weight of rats, it can prevent the progressive deterioration of glucose control and significantly reduce the glucose AUC in the IPGTT of GK rats, demonstrating a regulatory effect on blood glucose levels.
Treatment of neurological diseases: In animal models, it has significantly delayed the onset of EAE (Experimental Autoimmune encephalomyelitis) in a dose-dependent manner, reduced the severity of the neurological system, and shortened the duration of EAE, demonstrating its potential in the treatment of neurological diseases.
Immunomodulatory effect: It has profound anti-inflammatory and disease-modifying activity in the DSS-induced colitis environment, and has extensive and effective anti-inflammatory effects on bone marrow cells. It may help interfere with the autosecretory and paracrine stimulation of cytokines produced by macrophages and other immune cells in the inflammatory microenvironment.
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