Publications by authors named "William S Korinek"
Article Synopsis
- - AST-004 is a small molecule that targets adenosine receptors and shows promise for protecting the brain after strokes and injuries, aiming to assess its safety and how it's processed in the body during a phase I clinical trial on healthy individuals.
- - The study involved giving varying doses of AST-004 to different groups of participants and then analyzing its levels in blood, cerebrospinal fluid (CSF), and urine; no serious side effects were observed, though headaches were reported by some.
- - Findings indicated that AST-004 is safe at higher concentrations than previously effective in animal studies and that it reaches highest levels in CSF an hour after infusion, suggesting it may be suitable for further testing in treating strokes and brain injuries.
Article Synopsis
- AST-004 is a small molecule being researched as a cerebroprotectant for acute stroke, requiring evaluation of its interactions with the only current stroke treatment, tPA (alteplase).
- The study tested AST-004's stability and its effects on tPA's ability to break down clots using various in vitro methods, including assessing its performance in human blood.
- Results showed that AST-004 does not interact negatively with alteplase or tenecteplase, suggesting it can be safely administered alongside these treatments for stroke patients.
Background And Purpose: Treatment with A1R/A3R (adenosine A1 and A3 receptor) agonists in rodent models of acute ischemic stroke results in significantly reduced lesion volume, indicating activation of adenosine A1R or A3R is cerebroprotective. However, dosing and timing required for cerebroprotection has yet to be established, and whether adenosine A1R/A3R activation will lead to cerebroprotection in a gyrencephalic species has yet to be determined.
Methods: The current study used clinical study intervention timelines in a nonhuman primate model of transient, 4-hour middle cerebral artery occlusion to investigate a potential cerebroprotective effect of the dual adenosine A1R/A3R agonist AST-004.
Rapid phosphoester hydrolysis of endogenous purine and pyrimidine nucleotides has challenged the characterization of the role of P2 receptors in physiology and pathology. Nucleotide phosphoester stabilization has been pursued on a number of medicinal chemistry fronts. We investigated the in vitro and in vivo stability and pharmacokinetics of prototypical nucleotide P2Y receptor (P2YR) agonists and antagonists.
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