Plinabulin, a marine-derived small-molecule, is BeyondSpring’s lead asset and is currently in late-stage clinical development for the prevention of chemotherapy-induced neutropenia (CIN) and as an anticancer therapy in non-small cell lung cancer (NSCLC).
Mechanism of Action
Plinabulin activates GEF-H1, a guanine nucleotide exchange factor. GEF-H1 activates downstream transduction pathways leading to the activation of the protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells to up-regulate immune-related genes, which contributes to the up-regulation of a series of genes leading to dendritic cell maturation, T-cell activation and other effects that prevent neutropenia by reducing the neutrophil breakdown.
1 Chang et al., 2008 Mol Biol Cell; Kashyap et al., 2018 submitted.
2 Zhang et al., 2005 Mol Cell Biol.
3 Keystone Meeting, Mar 2017; Kashyap et al. 2018 submitted.
4 Singh et al., 2011 Blood.
5 Keystone Meeting, Mar 2017; Unpublished findings: University of Basel.
6 Keystone Meeting, Mar 2017.
7 Suwa et al., 2000 Am J Physiol Heart Circ Physiol; Ghosh et al., 2018 ACR Annual Conference; Blayney et al., Society of Leukocyte Biology abstract submitted.
8 Asensi et al., 2004 Infection and Immunity.