In summary, we proposed a new EC score function and exemplified its effectiveness with diverse biological targets. In some cases, we found that the new EC scores gives a linear relationship with bioactivity, while the traditional EC scores (Pearson's coefficients) do not. In certain cases where both showcased linear correlations with bioactivity, the new EC scores gave higher R 2 coefficients. To extend the application of EC scores to some cases where EC scoring has traditionally failed, we introduce two indices, esp_extre and sas_ratio. These two indices guide the selection of ligands or targets suitable for EC score ranking. Furthermore, we provided six rules where the EC score should be used in caution to rank the ligands.