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. Author manuscript; available in PMC: 2016 Dec 1.
Published in final edited form as: Cancer Lett. 2015 Sep 1;369(1):229–241. doi: 10.1016/j.canlet.2015.08.021

Figure 10.

Figure 10

Proposed VDA mechanism of action of OXi8007 in activated endothelial cells. Phosphate prodrug OXi8007 is cleaved by a non-specific phosphatase to OXi8006 that enters the endothelial cell and binds to tubulin resulting in microtubule depolymerization and RhoA activation. RhoA kinase (ROCK) is activated by RhoA and phosphorylates MLC and phosphorylates and inactivates MLC phosphatase (MP) leading to increased levels of phosphorylated MLC and activation of non-muscle myosin II which results in actin bundling and stress fiber formation. ROCK also leads to focal adhesion kinase (FAK) phosphorylation and activation contributing to increased focal adhesions.