Herein, we elucidate the in vitro mechanism of action of enitociclib, atuveciclib, and KB-0742 in MYC-driven DLBCL preclinical models and demonstrate that enitociclib treatment induces a depletion of MYC as well as describe novel CDK9 inhibitor target genes that are downregulated on a different time course to deliver an “oncogenic shock” (33, 34) in cells addicted to MYC expression. This evidence concerns the gene MYC and diffuse large B-cell lymphoma.