dBRD9A

dBRD9A is a small molecule proteolysis-targeting chimera (PROTAC) designed to selectively induce the degradation of Bromodomain-containing protein 9 (BRD9). BRD9 is a key subunit of the non-canonical BAF (ncBAF) chromatin remodeling complex, which is essential for maintaining the transcriptional program and growth of certain malignancies, including KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML). By depleting BRD9, dBRD9A disrupts the chromatin accessibility of super-enhancers for critical transcription factors such as IRF8 and MYC, leading to growth arrest and myeloid differentiation. Research indicates that dBRD9A remains effective in AML cells that have acquired resistance to MEN1 inhibitors, suggesting its potential as a therapeutic strategy for relapsed or refractory KMT2Ar leukemia.