Plinabulin

Plinabulin (NPI-2358) is a vascular disrupting agen (VDA) against tubulin-depolymerizing with an IC₅₀ of 9.8 nM against HT-29 cells^[1]. Plinabulin binds the colchicine binding site of β-tubulin preventing polymerization and has potent inhibitory to tumor cells^[2]. IC50 & Target: β-tubulin^[2] In Vitro: Plinabulin (NPI-2358) (2-200 nM; 30 minutes; HUVECs cells) is a potent anti-tumor agent which is active in multidrug-resistant (MDR) tumor cell lines, and is able to rapidly induce tubulin depolymerization and monolayer permeability in HUVECs, with IC₅₀ values of 18 nM for DU 145 cells; 13 nM for PC-3 cells; 14 nM for MDA-MB-231 cells; 18 nM for NCI-H292 cells; and 11 nM for Jurkat leukemia cells^[1]. In Vivo: Plinabulin (0 mg/kg-15 mg/kg; intraperitoneal injection; female CDF1 and C3H/He mice) induces a time- and dose-dependent decrease in tumor perfusion. The KHT sarcoma is more sensitive than the C3H tumor to the anti-tumor effects of Plinabulin, while radiation response is enhanced in both models^[3].