DB1976

DB1976 is a first-in-class, small molecule inhibitor of the transcription factor **PU.1** (encoded by the *SPI1* gene). PU.1 is a member of the ETS family of transcription factors and serves as a master regulator of myeloid and B-cell development and function. DB1976 specifically binds to the DNA-binding domain of PU.1, disrupting its interaction with DNA and subsequently downregulating the expression of pro-inflammatory cytokines and other downstream targets. In preclinical models, DB1976 has demonstrated efficacy in alleviating atherosclerosis by suppressing the IL-1β/NF-κB signaling pathway, reducing reactive oxygen species (ROS) levels, and inhibiting apoptosis in macrophages. Beyond cardiovascular applications, it is also being investigated for its potential in treating hematological malignancies, such as acute myeloid leukemia (AML), where PU.1 activity is often dysregulated.

Other names

PU.1 inhibitor DB1976