2. 化合物評価
  3. 細胞株パネルを用いた化合物の作用機作の評価

Evaluation of modes of action of compounds using cell line panel

(担当:旦 慎吾)
(Member in charge: Shingo Dan)



This evaluation system has long been used for estimating the modes of action of compounds that cause cell growth inhibition. Using JFCR39, a panel of 39 cancer cell lines derived from various tissues of origin (7 from lung cancers, 6 from gastric cancers, 5 from colon cancers, 5 from ovarian cancers, 6 from central nervous system (CNS) cancers, 5 from breast cancers, 2 from renal cancers, 2 from prostate cancers and 1 from melanoma), the concentration at which the test compound causes half growth inhibition (GI50) in each of the cell lines is measured, and the fingerprint, or the spectrum of GI50 concentrations across the JFCR39 panel, is used to predict its mode of action. It has been clarified that compounds with a common mechanism of action show fingerprints similar to each other. In this system, prediction of the mode of action of a compound is accomplished by comparing its fingerprint with those of >250 reference compounds including anticancer drugs and other physiologically active substances with known modes of action. Since this system is a cell-based assay, it is also useful to evaluate the target specificity of a novel molecule-targeted drug found in a cell-free screening system.



Each cell line of the JFCR 39 panel is plated in a 96-well plate, and the dilution series of the test compound (usually at a final concentration of 10-8 to 10-4 mol / L) is added the following day. After 2 days of culture, cell proliferation is estimated colorimetrically by measuring A525 in each well stained with sulforhodamine B. The concentration of the compound that inhibit cell proliferation to 50% (GI50) is calculated from the dose response curve, and the deviation of log GI50 in each cell line to the average log GI50 across the JFCR39 is determined and displayed as a fingerprint.

Evaluation of compounds

JFCR39パネルの細胞株のうち、被験化合物が最も効きやすい細胞株と効きにくい細胞株のlog GI50の差(Range)、および、log GI50の平均値と最も効きやすい細胞株のlog GI50の差(delta)を計算し、それぞれ1以上、0.5以上の場合、薬効の差が大きい(Differential Activity/DA (+))と判定する。また、測定したフィンガープリントを、およそ250種類の標準物質のフィンガープリントと比較することにより、作用機作の推定あるいは作用機作の新規性の評価を行う。

To evaluate the differential activity of a compound across the JFCR39 panel, we calculated the difference between log GI50 in the most sensitive cell line and the least sensitive cell line (Range) and the difference between log GI50 in the most sensitive cell line and the average GI50 across the JFCR39 (Delta). The criteria that the test compound has the differential activity, or DA(+), is “Range≧1 and Delta≧0.5”. To predict the mode of biological action of a test compound, its fingerprint is subjected to “COMPARE analysis”, or comparing it with those of approximately 250 reference compounds in the database. If it is similar to a certain reference compound, its mode of action is supposed to be similar to the reference compound. If it does not exhibit similarity to any of the reference compounds, the test compound is supposed to have a unique mechanism of action.

Desired information (if available)


The concentration of the compounds and time of exposure required for cell growth inhibition.


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