ENMD-1198 inhibits the proliferation of endothelial cell HMEC-1 and BMH29L (IC50: 0.4 μM and 3.8 μM) and it also significantly inhibits capillary tube formation from 0.1 μM and suppresses endothelial cell morphogenesis at 1 μM. ENMD-1198 inhibits endothelial cell motility and endothelial cell migration and inhibits MDA-BO2 cancer cell viability (IC50: approximately 0.8 μM). ENMD-1198 also inhibits the phosphorylation of MAPK/Erk, PI-3K/Akt, and FAK. ENMD-1198 (0.5 μM) inhibits the formation of capillary tubes in HMEC-1 cells. Moreover, ENMD-1198 at the IC50 for cell proliferation causes a significant decrease in VEGFR-2 expression both in the presence and in the absence of serum. ENMD-1198 rapidly causes extensive microtubule depolymerization and accumulation of actin stress fibers and large focal adhesions [1]. ENMD-1198 has both an antiangiogenic effect and a vascular disruptive effect in vitro. ENMD-1198 reduces the viability of RAW264.7 osteoclast precursor cells and inhibits PTHrP-stimulated bone resorption. ENMD-1198 shows inhibitory activity against RAW264 (IC50: approximately 0.4 μM) and is shown to be 4 times more potent than 2ME2 (IC50 appro 1.6 μM) [2]. The activation of HIF-1α and STAT3 is dramatically reduced by ENMD-1198, which leads to lower VEGF mRNA expression. In addition, the tumor cell migratory and invasive properties are obviously inhibited [3].

ENMD-1198 treatment protects the bone against tumor-induced osteolysis in vivo [2]. ENMD-1198 (200 mg/kg/d, peroral gavage)-based combination treatments decrease tumor burden but do not eradicate the tumor in mice. ENMD-1198 (200 mg/kg/day, p.o.) leads to a significant reduction in tumor growth, tumor vascularization, and numbers of proliferating tumor cells [3].