83375-00-2Relevant academic research and scientific papers
Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease
Dai, Baozhu,Ma, Xingxing,Tang, Yadong,Xu, Le,Guo, Su,Chen, Xinyan,Lu, Shitong,Wang, Guangjie,Liu, Yajing
, (2020/12/09)
Ryanodine receptors (RyRs) are important ligand-gated Ca2+ channels; their excessive activation leads to Ca2+ leakage in the sarcoplasmic reticulum that may cause neurological diseases. In this study, three series of novel potent RyR1 inhibitors based on dantrolene and bearing semicarbazone and imidazolyl moieties were designed and synthesized, and their biological activity was evaluated. Using a single-cell calcium imaging method, the calcium overload inhibitory activities of 26 target compounds were tested in the R614C cell line, using dantrolene as a positive control. The preliminary investigation showed that compound 12a suppressed Ca2+ release as evidenced by store overload-induced Ca2+release (SOICR) (31.5 ± 0.1%, 77.2 ± 0.1%, 93.7 ± 0.2%) at 0.1 μM, 3 μM and 10 μM, respectively. Docking simulation results showed that compound 12a could bind at the active site of the RyR1 protein. The Morris water-maze test showed that compound 12a significantly improved the cognitive behavior of AD-model mice. Further studies on the structural optimization of this series of derivatives are currently underway in our laboratory.
KINASE INHIBITOR
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Paragraph 0161; 0162, (2021/04/16)
The present invention aims to provide a novel kinase inhibitor and the like, and a therapeutic agent for a disease, a drug discovery screening method and the like utilizing such inhibitor and the like. The compound represented by the following formula (I) and a salt thereof can inhibit plural kinases including LATS (particularly LATS2) which is the major kinase in the Hippo signal transduction pathway. In addition, diseases or tissue damage associated with failure of cellular proliferation can be treated. Therefore, the present invention is beneficial, for example, in the research field of cell functions and diseases, in which the Hippo signal transduction pathway is involved, and the like. Furthermore, it is beneficial in the medical field for the treatment of such diseases and the like. wherein each symbol is as defined in the DESCRIPTION.
ADDITIVE COMPOSITION FOR CULTURE MEDIUM, ADDITIVE COMPOUND FOR CULTURE MEDIUM, AND METHOD FOR CULTURE OF CELLS OR TISSUE USING SAME
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Paragraph 0144-0145, (2020/06/15)
The present invention provides a medium additive composition containing a compound represented by the following formula (I), or a salt thereof: {wherein each symbol is as defined in the DESCRIPTION.}
