Our previously reported tricyclic dihydropyrazinoindoloneseriesof Mcl-1 inhibitors, such as compound 9, demonstratedexcellent affinity for the Mcl-1 protein (Ki < 200 pM in time-resolved fluorescence resonanceenergy transfer (TR-FRET) binding assay) and highly selective antiproliferativeactivities in the Mcl-1-sensitive multiple myeloma cell line NCI-H929(9, GI50 = 120 nM).88 The series also induced caspase activation in cancer cells in goodcorrelation with Mcl-1 binding affinity to prove the inhibitory mechanismof action. This evidence concerns the gene MCL1 and cancer.