DB2115

DB2115 is a novel small molecule transcription factor redistributor that targets the transcription factor PU.1, which is frequently corrupted in acute myeloid leukemia (AML). It functions by competitively inhibiting the interaction between PU.1 and DNA. Unlike traditional inhibitors that aim for global suppression, DB2115 induces a cistromic repositioning of PU.1 chromatin binding, leading to the reduction of canonical PU.1 transcripts and the activation of alternative, non-canonical PU.1-driven gene networks. This pharmacological rewiring of transcriptional circuits promotes the differentiation of AML cells down the myeloid lineage. The compound was developed through a collaboration involving researchers at the Albert Einstein College of Medicine and Georgia State University.