Roche Real-Time Cell Analysis System Provides Predictive Mechanism Information for Small Molecule Studies

Roche xCELLigence Real-Time Cell Analysis System Provides Predictive Mechanism Information for Small Molecule Compound Studies

Research breakthroughs on which protein target sites a drug or small molecule compound can modulate are constrained by a number of factors, including the level of expression of the target protein, the effective concentration of the compound, and the time required for the compound to interfere with the target protein. One limitation of the current multidimensional phenotypic profiling method is that usually only one time point is selected to evaluate the effects of the compound. Therefore, the relevant conclusions about the mechanism of action of the compounds obtained according to this method are based only on the specific time points at which the samples are processed.

To overcome these limitations, Abassi other researchers have developed ^a method of living cells effect curve for dynamic monitoring of the effect of small molecules, the method uses xCELLigence System Roche Applied Science, enabling real-time monitoring of a cell. The method was tested by screening a drug library containing FDA approved drugs, test compounds, and natural compounds. The time-dependent Cell Response Profiles (TCRPs) based on impedance detection produced by similarly active compounds are also very similar; the compounds can be divided into different clusters according to the similarity of TCRP.

Through this technology, researchers have identified a new mechanism of action of existing drugs, in addition to the calcium-modulating activity of the previously reported COX-2 inhibitor Celecoxib, and also found another mechanism of the experimental compound Monastrol. . The researchers also identified a new anti-mitotic agent and defined its characteristics. This method will also help detect off-target effects of a particular compound.

The TCRP technique described by Abassi et al. effectively overcomes the limitations of current universal methods in terms of time dependence. When used in conjunction with cell number, morphology, and adhesion, TCRP technology can significantly expand the "biospace" of the compound being screened. This technology provides ample opportunity to detect and identify small molecule-related biological activities.

In summary, these studies show that the time-based solution provided by the TCRP method can be used in conjunction with phenotypic profiling to obtain more data related to small molecule compounds. The TCRP method provides predictive mechanism information for small molecule compounds.

About label-free cell detection technology

As an innovation in the field of label-free biometrics, Roche's Department of Applied Science's xCELLigence system provides a new cell analysis and detection platform that requires no labeling and real-time monitoring of cells. The cells are seeded in an E-Plate microplate with an embedded microelectronic sensor at the bottom of each well. The microelectrode impedance is mainly determined by the point and surrounding ion environment. A baseline can be measured when the electric field is applied to it. Impedance, the presence or absence of cells, and changes in the degree of adherence affect the passage of electrons and ions on the surface of the electrode sensor. Therefore, the adherence, adhesion, growth, etc. of the cells on the E-Plate microplate assay plate correspond to the impedance measured by the sensor. The index obtained from the impedance reflects the cell biological state such as cell proliferation, survival, apoptosis, and morphological changes. (Roche Applied Science)

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references:( Reference full text download address)
(1) Abassi YA et al.: Kinetic cell-based morphological screening: prediction of mechanism of compound action and off-target effects. Chem Biol 2009; 16:712-723