Stroke Drug Development Targeting Necroptosis

Studies have identified a number of specific pathological processes and proteins in necroptosis. Therefore, it is an important research strategy to regulate these pathological processes and proteins and thus achieve a therapeutic effect on stroke. Although proteins such as the tumor necrosis factor (TNF) family play an important role in necrophagy, they are not used as a target for regulating necroptosis because they are involved in various physiological and pathological activities of the body. Therefore, Ace Neuroscience offers a comprehensive service to accelerate the development of stroke drugs targeting necroptosis.

Stroke Drug Development Targeting Necroptosis

Target Identification & Validation

Although some important targets have been identified in the process of necrotizing targeting, we need to further explore the specific pathological process of necroptosis and find more specific targets to increase the chance of successful stroke drug development.

We construct a target identification and identification platform for necroptosis process, and provide different in vitro and in vivo models of necroptosis to ensure the accuracy and scientificity of the study.

Screening & Validation of Necroptosis Regulators

RIP1, RIP3, and MLKL are proteins specific to necroptosis. Therefore, screening for necroptosis regulators against these three proteins has a very high specificity for treating stroke by regulating necroptosis. With this in mind, Ace Neuroscience has established a specific virtual screening platform to screen for regulators targeting these three protein-related pathways.

  • Based on our ultra-large small molecules library, including compound libraries, natural product libraries, and fragment libraries, we construct the virtual screening platform to obtain necroptosis regulators.
  • We validate the modulatory effects of candidate regulators on necroptosis through in vitro and in vivo necroptosis experimental models.
  • We assess the therapeutic effects of candidate inhibitors on stroke by building different in vitro and in vivo stroke models.

Preclinical Evaluation of Drug Candidates for the Treatment of Stroke

Preclinical pharmacological activity evaluation of the screened candidate necroptosis modulators against stroke is performed to determine the therapeutic effects and specific mechanisms of action of the candidates against stroke. Ace Neuroscience provides a comprehensive pharmacological activity evaluation and pharmacokinetic evaluation service to accelerate your stroke drug development studies targeting necrotizing apoptosis.

  • We provide different in vitro and in vivo stroke models to validate the efficacy of necroptosis regulators on stroke and to further explore the mechanism of action of necroptosis.
  • We offer qPCR, ELISA, WB, and other gene or protein assays for different biomarkers of the necroptosis process, such as RIP and RIP3 kinases, phospho-RIP, and phospho-RIP3 kinases, MLKL, caspase-8, and inflammatory factors.
  • We verify necroptosis by plasma membrane integrity assay, cellular inclusions assay, and mitochondrial membrane potential assay.
  • We detect protein interactions by yeast two-hybrid system, phage display technique, immunoprecipitation technique and other methods.

In addition, we provide other services related to the development of stroke drugs targeting necroptosis process. If you would like to learn more about our services, please feel free to contact us.

References
  1. Jun-Long, H., et al. Necroptosis signaling pathways in stroke: From mechanisms to therapies. Curr Neuropharmacol. 2018, 16(9): p.1327-1339.
  2. Hribljan, V., et al. Necroptosis is one of the modalities of cell death accompanying ischemic brain stroke: From pathogenesis to therapeutic possibilities. Croat Med J. 2019, 60(2): p.121-126.
All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
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