BBI-355 + BBI-825

BBI-355 + BBI-825 is a **combination therapy** under development for the treatment of solid tumors harboring oncogene amplification, especially those characterized by high levels of extrachromosomal DNA (ecDNA). BBI-355 is a *CHK1 inhibitor* that disrupts the DNA damage response and cell cycle checkpoint regulation, while BBI-825 is a *selective ribonucleotide reductase (RNR) inhibitor* that impairs deoxyribonucleotide synthesis, thereby blocking DNA replication and repair. When combined, these agents synergistically induce replication stress and mitotic catastrophe in cancer cells that rely on amplified oncogenes and ecDNA, resulting in cancer cell death. This combination has demonstrated synergistic cytotoxicity in preclinical cancer cell lines and tumor regression in mouse models. They are developed by Boundless Bio for oral administration, with clinical development planned for 2025[1][5][7].