Stroke Drug Development Targeting Heat Shock Protein 70

Heat stress proteins (HSP) regulate a variety of signaling pathways, including programmed cell death, neuroinflammation and immune response. Among all kinds of heat stress proteins, heat stress protein 70 (HSP70) has been studied most extensively, which can regulate stroke pathology by regulating brain damage, necroptosis, and blood-brain barrier permeability after stroke. Studies have shown that upregulation of HSP70 can effectively mitigate the damage caused by stroke. However, the research direction is more limited. Therefore, Ace Therapeutics offers comprehensive services to accelerate the development of stroke drugs targeting HSP70 protein.

Fig.1 Structure of heat shock protein 70.

Screening of Heat Stress Protein 70 Modulators

HSP70 can regulate various activities of the body, including various activities of proteins, cell death, immunity, inflammation, oxidative stress and so on. It also plays an important role in the pathological process of stroke. The current study suggests that HSP70 can mitigate the harm of stroke by regulating the cell death process and enhancing anti-inflammatory capacity. Therefore, the effective screening of HSP70-targeting modulators is the first step in the development of stroke drugs targeting HSP70.

• Based on our small molecule library, including ultra-large compound library, natural product library, and fragment library, we have established a high-throughput platform to rapidly screen regulators that can effectively modulate HSP70.
• We validate the effects of candidate modulators on HSP70 in vitro and in vivo stroke models with HSP70 overexpression or deficiency, such as manipulation of HSP70 expression by viral vector-mediated overexpression, siRNA-mediated downregulation, or by induction of sublethal heat stress.

Preclinical Evaluation of Drug Candidates for the Treatment of Stroke

After screening and validating HSP70 modulators, Ace Therapeutics provides comprehensive services to further investigate the preclinical pharmacologic evaluation of modulators in stroke.

• We provide different in vitro and in vivo stroke models to evaluate the pharmacological activity of candidate modulators against stroke.
• We explore the dose-effect and time-effect relationships of candidate modulators for stroke to determine more appropriate drug addition.
• We provide protein microarray and gene microarray services to evaluate the effects of candidate modulators on different pathways.
• We use western blotting, ELISA, and immunohistochemistry assays to quantify and localize different proteins.

HSP70 can regulate a variety of pathological pathways and affect the pathological process of stroke. Therefore, the development of stroke drugs targeting HSP70 is an effective way to treat stroke. If you would like to learn more about our services, please feel free to contact us.

1. Kim, J.Y., et al. The 70-kda heat shock protein (hsp70) as a therapeutic target for stroke. Expert Opin Ther Targets. 2018, 22(3): p.191-199.