Sabizabulin
Sabizabulin is an orally bioavailable, small molecule tubulin inhibitor, with potential antineoplastic, antiviral and anti-inflammatory activities. Upon oral administration, sabizabulin binds to the colchicine-binding site of alpha- and beta-tubulin subunits of microtubules and crosslinks the microtubules, thereby inhibiting microtubule polymerization in tumor blood vessel endothelial cells and tumor cells. This blocks the formation of the mitotic spindle and leads to cell cycle arrest at the G2/M phase. As a result, this agent disrupts the tumor vasculature, tumor blood flow, deprives tumor cells of nutrients, and induces apoptosis. In addition, as microtubules plays an important role in intracellular transport, the inhibition of its polymerization may disrupt the transport of the androgen receptor (AR) into the cell nucleus, as well as virus trafficking around the cell. This may decrease viral replication and assembly. Inhibition of tubulin polymerization may also inhibit the release of pro-inflammatory cytokines and disrupt inflammatory cell activities. Sabizabulin is not a substrate of P-glycoprotein (Pgp), an efflux pump that when overexpressed, may confer resistance to taxane agents.