CBPD-409

CBPD-409 is a small molecule degrader, likely a proteolysis-targeting chimera (PROTAC), that targets the paralogous transcriptional coactivators and histone acetyltransferases CBP (CREB-binding protein) and p300 (EP300). These proteins are essential for the transcriptional programs of key oncogenes in prostate cancer, including the androgen receptor (AR) and MYC pathways. By inducing the selective proteasomal degradation of CBP and p300, CBPD-409 disrupts oncogenic signaling and inhibits tumor growth. Preclinical research, particularly in syngeneic mouse models, has demonstrated that CBPD-409 can sensitize otherwise non-responsive "cold" prostate tumors to immune checkpoint blockade (e.g., anti-PD-1 therapy). Combination treatment has been shown to yield overt tumor regression and a robust lymphocytic response involving CD4+, CD8+, and NK cells. The compound was developed and studied by researchers at the University of Michigan.