High throughput measurement of Ca++ dynamics in human stem cell-derived cardiomyocytes by kinetic image cytometry: a cardiac risk assessment characterization using a large panel of cardioactive and inactive compounds was written by Lu, Hua Rong;Whittaker, Ross;Price, Jeffrey H.;Vega, Raquel;Pfeiffer, Emily R.;Cerignoli, Fabio;Towart, Rob;Gallacher, David J.. And the article was included in Toxicological Sciences in 2015.Reference of 119431-25-3 This article mentions the following:
Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as a powerful in vitro model for cardiac safety assessment which may allow for better identification of compounds with poor arrhythmogenic liability profiles early in the drug discovery process. Here, we describe our examination of the Kinetic Image Cytometer (KIC) system’s ability to predict adverse compound effects using hiPS-CMs and a library of 53 compounds, the majority of which are known to be cardioactive compounds, and several neg. controls. The KIC provides a high throughput method for analyzing intracellular calcium transients. In the cardiomyocyte, intracellular calcium transients integrate the electrochem. signals of the action potential (AP) with the mol. signaling pathways regulating contraction. Drug-induced alterations in the shape and duration of AP result in changes to the shape and duration of the intracellular calcium transient. By examining calcium transient dynamics in hiPS-CMs, KIC can be used as a phenotypic screen to assess compound effects across multiple ion channel types (MITs), detecting MITs, calcium handling and signaling effects. The results of this blinded study indicate that using hiPS-CMs, KIC is able to accurately detect drug-induced changes in Ca2+ transient dynamics (ie, duration and beat rate) and therefore, may be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. In the experiment, the researchers used many compounds, for example, 1-(4-Chlorophenyl)-2-(4-(4-fluorobenzyl)piperidin-1-yl)ethan-1-ol (cas: 119431-25-3Reference of 119431-25-3).
1-(4-Chlorophenyl)-2-(4-(4-fluorobenzyl)piperidin-1-yl)ethan-1-ol (cas: 119431-25-3) belongs to piperidine derivatives. Piperidine is a saturated organic heteromonocyclic parent, an azacycloalkane, a secondary amine and a member of piperidines. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Reference of 119431-25-3
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem