GL0385

GL0385 is a small-molecule direct activator of the pro-apoptotic protein Bax (Bcl-2-associated X protein) developed for the treatment of breast cancer, including triple-negative breast cancer (TNBC) and estrogen receptor (ER)-negative breast cancer (ENBC). It was discovered through structural optimization of the progenitor Bax activators SMBA1 and CYD-2-11 by researchers at the University of Texas Medical Branch, Louisiana State University Health Sciences Center, and MD Anderson Cancer Center. GL0385 specifically targets the Ser184 residue of Bax, preventing its phosphorylation and promoting its translocation to the outer mitochondrial membrane. This translocation triggers Bax oligomerization, leading to mitochondrial outer membrane permeabilization (MOMP), cytochrome c release, caspase-3 activation, and PARP cleavage, which ultimately induces apoptosis in cancer cells. In preclinical models, GL0385 has demonstrated potent anti-proliferative, anti-migratory, and anti-invasive activities, as well as significant in vivo efficacy in suppressing breast cancer xenograft tumor growth.