Description
AI-10-49 is an inhibitor that binds the transcription factor fusion CBFbeta-SMMHC. AI-10-49, that selectively binds to CBFbeta-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv (16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFbeta-SMMHC fusion protein may be an effective therapeutic approach for inv (16) AML, and they provide support for transcription factor targeted therapy in other cancers