NPI-1387

NPI-1387 is a synthetic small molecule vascular disrupting agent (VDA) originally developed by Nereus Pharmaceuticals. Derived from marine-based chemical scaffolds, it is designed to selectively target and destabilize the established vasculature of solid tumors. The drug functions by binding to the colchicine site of tubulin, thereby inhibiting tubulin polymerization and disrupting the microtubule cytoskeleton within endothelial cells. This action leads to rapid morphological changes in the immature endothelial cells of tumor blood vessels, resulting in increased vascular permeability, blood flow stasis, and subsequent hemorrhagic necrosis of the tumor core. Unlike anti-angiogenic therapies that inhibit the formation of new vessels, NPI-1387 is intended to destroy existing tumor blood supply while sparing mature vessels in healthy tissues. It was primarily investigated in Phase 1 clinical trials for advanced solid tumors, though development was ultimately terminated.