For example, the original lead compound with Ki of 86 nM and an IC50 of 830 nM was optimized by adding fluorine to the chlorophenyl ring mimicking Phe19, producing MI-63 with Ki of 3 nM and IC50 of 280 nM [42], and activating the wild-type p53 pathway and apoptosis in cancer cell lines but proving unsuitable for pre-clinical studies in vivo. This evidence concerns the gene TP53 and cancer.