Fig. 2

a-1 When compounds were screened in vitro in the MNT without γH2AX evaluation, 26 out of 28 drug candidates showed positive, which could have resulted in the withdrawal of 26 candidate compounds. a-2 On the other hand, when they were screened in the MNT with γH2AX evaluation, none of the 26 candidates showed γH2AX induction; therefore, all the candidates were suggested to be aneugens and were transferred to the next development stage without being withdrawn. b The scatter plots show the relationship between micronucleus induction and pharmacological efficacy. The vertical axis represents the potency of micronucleus induction, defined as the negative log of the dose that provided the maximum frequency of micronuclei. The horizontal axis shows the pharmacological efficacy, defined as the negative log of the 50% inhibitory concentration (IC₅₀) on target enzyme activity. A high correlation of micronucleus induction with pharmacological efficacy suggested that the MoA of induction was related to an on-target pharmacological effect. Since the intended indication of the drug candidates was anti-tumor, the on-target effect was assumed not to be a drawback in drug development