Ischemia-Reperfusion
Ischemia-reperfusion (I/R) injury describes the intricate pathological process that transpires when the blood supply is re-established to the tissues after a period of being starved of oxygen and nutrients. Reperfusion, while necessary to ensure the survival of tissues, sets off a cascade of events that are damaging, worsening cellular and organ injury. Protheragen is dedicated to pioneering innovative compounds and therapeutic strategies that target the MyD88 pathway, aiming to address the critical unmet needs in the research and preclinical development of solutions for ischemia-reperfusion injury.
Overview of Ischemia-Reperfusion
Ischemia-reperfusion injury is the more accurate description of the damage that is caused it is not the result of the ischemic event only. The damage is essentially the result of reintroducing blood supply to the ischemic area and the reoxygenation that follows. The phenomenon presents in diverse clinical settings such as myocardial infarction, stroke, organ transplantation, and shock. While re-perfusion is necessary for survival, it is often a double-edged sword, as it unleashes damaging reactive oxygen species, pro-inflammatory molecules, and immune cell recruitment that results in necrosis and, to a lesser extent, apoptosis and dysfunction of the organ involved.
MyD88 in Ischemia-Reperfusion Pathogenesis
The pathogenesis of ischemia-reperfusion injury involves a multitude of factors including oxidative stress, mitochondrial injury, vascular endothelium injury, and inflammation. One of the key components in these systems and the injury processes is Myeloid Differentiation Primary Response 88 (MyD88). MyD88 is an essential adaptor protein for the signal transduction processes occurring downstream of the majority of Toll-like Receptors (TLRs).
Fig.1 The underlying mechanism of MyD88's involvement in CIRI. (Yang, J., et a.., 2021)MyD88 is known to link the TLR and IL-1R signaling pathways to I/R injury. TLR and IL-1R pathways are known to trigger inflammatory pathways via MyD88. When blood flow is restored, TLRs are stimulated and MyD88 dependent pathways are activated as a result of DAMPs (damage associated molecular patterns). This, in turn, results in an increase of TNF-α, IL-1β, and IL-6, which are known to cause inflammation in myocardial infarction and stroke. MyD88 is believed to be a good target to control inflammation and I/R injury.
Targeting MyD88 for the Therapeutic Development in Ischemia-Reperfusion
| Drug Name | Indication | Mechanism of Action | Key Progress | Development Stage |
| Peptide Mimetic (M20) | Inflammatory lung disease (incl. I/R) | Inhibits MyD88 dimerization, blocks IRAK1/4 recruitment to suppress TLR/MyD88 signaling | Reduces I/R-related inflammation; dampens innate immune responses | Preclinical |
| Eritoran | Cardiac/Lung I/R injury | TLR4 antagonist blocking MyD88-dependent signaling | Attenuates myocardial I/R injury; TLR4/MyD88 identified as key driver in lung I/R | Preclinical |
| Liproxstatin-1 | Cerebral/Cardiac I/R injury | Inhibits ferroptosis (synergizes with TLR/MyD88 pathway); reduces lipid peroxidation | Indirect TLR/MyD88 crosstalk; applicable for multi-organ I/R protection | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers integrated, end-to-end services to derive novel MyD88-targeted compounds and therapies for ischemia-reperfusion injury. With advanced technologies, our expert scientists shorten the discovery and preclinical development timelines and provide bespoke services in therapeutic discovery and disease model development aligned with the exact specifications of your project.
MyD88-Targeted Ischemia-Reperfusion
In regard to MyD88-dependent ischemia-reperfusion injuries, Protheragen leads the discovery and development of therapeutics. Our team's deep knowledge of the unique pathological profile of each condition enables Protheragen to tailor solutions for the following ischemic injuries, resulting in rapid translation from concept to application:
- Myocardial Infarction (MI)
- Hepatic Ischemia-Reperfusion Injury
- Stroke
- Renal Ischemia-Reperfusion Injury
Therapeutic Discovery Platform for Ischemia-Reperfusion
Protheragen's robust therapeutic discovery services encompass the entire spectrum of drug discovery and preclinical advancement, with a specific emphasis on MyD88-related targets:
Disease Models Development for Ischemia-Reperfusion
For the precise assessment of MyD88-targeted therapeutic candidates' efficacy and safety, Protheragen provides a wide array of advanced disease model development services:
Protheragen specializes in providing one-stop preclinical development services dedicated to advancing MyD88-targeted therapeutics for Ischemia-Reperfusion. Our end-to-end solutions streamline the drug development process, from disease model development to in-depth pharmacokinetics and drug safety evaluation. Other focuses include investigator-initiated trials aimed at expediting the primary assessment stage.
If you are interested in our services, please don't hesitate to contact us.
References
- Braza, F., et al. "Role of Tlrs and Damps in Allograft Inflammation and Transplant Outcomes." Nat Rev Nephrol 12.5 (2016): 281-90.
- Yang, J., et al. "Dexmedetomidine Resists Intestinal Ischemia-Reperfusion Injury by Inhibiting Tlr4/Myd88/Nf-Kappab Signaling." J Surg Res 260 (2021): 350-58.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.