Stroke Drug Development Targeting Pyroptosis

Pyroptosis is an inflammatory caspase-induced lytic cell death. The normal operation of pyroptosis requires the regulation of many specific proteins, such as the inflammasome and gasdermin protein family. The occurrence of pyroptosis triggers an inflammatory response, oxidative stress, and other pathological processes that exacerbate the damage to brain tissue in the stroke. Therefore, targeting these specific proteins to inhibit pyroptosis and thus achieve stroke treatment is a potential therapeutic way. Ace Therapeutics provides a complete service to develop therapeutic agents for stroke targeting specific proteins in pyroptosis.

Target Identification & Validation

It has been shown that NLRP1 inflammasome, NLRP3 inflammasome, AIM2 inflammasome, NLRC4 inflammasome, and gasdermin protein family are all specific proteins in the process of pyroptosis. However, since the current understanding of pyroptosis is limited, we still need to discover more targets to better serve the development of stroke drugs targeting pyroptosis.

• We perform high-throughput screening of candidate targets for pyroptosis-related pathways in stroke based on genomics, proteomics, and proteomics platforms.
• We build in vitro and in vivo models of target expression aberrations by drug administration and genetic manipulation to assess the role of candidate targets.
• We investigate the mechanism of action of candidate targets through gene expression profiling, signaling pathway studies, and bioinformatics analysis.

High Throughput Screening of Pyroptosis Inhibitors

After screening for potential targets of pyroptosis in stroke, a high-throughput screen for inhibitors against these targets was performed to identify drugs with potential therapeutic activity against stroke. Thus, Ace Therapeutics provides a platform for high-throughput screening against pyroptosis inhibitors, as well as experimental models of pyroptosis to validate the effects of candidate inhibitors.

• Based on our small molecule library, including ultra-large compound library, natural product library, and fragment library, we have established different high throughput screening platforms for targets and known pyroptosis inhibitors.
• We offer chemical modifications for potential pyroptosis inhibitor candidates to make them safer and more stable.
• We provide in vitro and in vivo models related to pyroptosis to validate the effect and mechanism of action of the inhibitor.

Preclinical Evaluation of Drug Candidates for the Treatment of Stroke

We have demonstrated the inhibition of pyroptosis by candidate pyroptosis inhibitors. Immediately after, we offer various pharmacological activity assessment services to test the efficacy of candidate pyroptosis inhibitors against stroke.

• We offer different in vitro and in vivo stroke models to validate the therapeutic efficacy of pyroptosis inhibitors against stroke and to further explore the mechanism of action of pyroptosis.
• We investigate the effects of candidate inhibitors on pyroptosis-related signaling pathways by molecular co-expression correlation, molecular interaction, molecular localization, activity, conformation, and other assays.
• We assess pyroptosis by scanning electron microscopy to observe cell morphology, western blotting to detect the expression of gasdermin D, and detecting the expression levels of caspases and pro-inflammatory factors.

If you would like to learn more about our services, please feel free to contact us.

1. Kesavardhana, S., et al., Caspases in cell death, inflammation, and pyroptosis. Annu Rev Immunol, 2020. 38: p. 567-595.
2. Gou, X., et al., Pyroptosis in stroke-new insights into disease mechanisms and therapeutic strategies. J Physiol Biochem, 2021. 77(4): p. 511-529.