CYD-2-11

CYD-2-11 is a small molecule Bax activator designed to target the S184 structural pocket located in the C-terminal tail of the Bax protein. By binding to this specific site, it triggers the proapoptotic activity of Bax, leading to programmed cell death in cancer cells. Beyond its direct role in apoptosis, CYD-2-11 has been found to induce the release of cytosolic DNA, which subsequently activates the cGAS-STING-TBK1-IRF3 signaling pathway. This activation results in the upregulation of PD-L1 and the production of type I interferons (IFN-alpha and IFN-beta) and pro-inflammatory chemokines such as CCL5 and CXCL10. Preclinical studies in mutant KRAS-driven non-small cell lung cancer (NSCLC) models demonstrate that CYD-2-11 synergizes with anti-PD-L1 immunotherapy by increasing the infiltration of cytotoxic T cells and reducing immunosuppressive cell populations, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs).