CBL0137 is an anticancer agent that activates p53 and suppresses NF-kB via trapping of the FACT (facilitates chromatin transcription) complex, an important histone chaperone that mediates nucleosome disassembly and reassembly and facilitates DNA transcription, replication, and repair.1,2 Importantly, it is able to intercalate DNA and disrupt DNA/histone interactions without genotoxicity. CBL0137 inhibits the self-renewal of cancer stem cells via NOTCH1 activation.3 CBL0137 downregulation of HSF1 and MYC(N) have also been demonstrated in animal models.4,5 CBL0137 has also been shown to improve immunological tumor control via facilitating release of cytokines and chemokines attracting NK, CD8+, and CD4+ T cells.6 CBL0137 was able to activate the Z-RNA sensor ZBP1 inducing necroptosis and reversing immune checkpoint blockage unresponsiveness in mouse models of melanoma.7
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