MOAs of Anti-cancer
Plinabulin is a GEF-H1 activator. Plinabulin destabilizes microtubule networks in the cellular cytoskeleton and releases the guanine nucleotide exchange factor, GEF-H1, which activates downstream signal transduction pathways, leading to the activation of c-Jun. Activated c-Jun enters the nucleus of dendritic cells, or DC, to up-regulate immune-related genes, which contributes to the up-regulation of a series genes leading to DC maturation, T cell activation and neutropenia prevention effects. Other microtubule destabilizing agents, such as the CA4P class, or microtubule stabilizing agents, such as docetaxel, do not induce DC maturation or neutropenia prevention. The elucidation of this mechanism was a 3-year collaborative effort among BeyondSpring, University of Basel and Massachusetts General Hospital.