ATN-161, a novel integrin α5β1 antagonist, inhibits angiogenesis and the growth of liver metastases in a murine model.

The combination of ATN-161 and 5-FU markedly diminishes tumor cell growth and significantly enhances the percentage of apoptotic (TUNEL-positive) tumor cells better than either control or single-agent treatments. Contrarily, treatments involving only a single agent do not elevate levels of TUNEL-positive tumor cells. Moreover, ATN-161 alone achieves a notable reduction in endothelial cell (EC) count by 21% after 48 hours, underscoring its potency against the control [1]. Furthermore, while ATN-161 effectively obstructs VEGF-induced migration and capillary tube formation in human coronary endothelial cells (hCECs), it does not affect their proliferation. Notably, ATN-161 progressively decreases VEGF-stimulated cell migration in a dose-dependent fashion, starting at 100 nM, thereby demonstrating significant efficacy (P<0.001 versus VEGF group) [2].

Preliminary experiments on α5β1-negative human colon cancer xenografts (HT29) demonstrate that ATN-161 treatment significantly diminishes both tumor weight and vessel density [1]. Furthermore, administering ATN-161 following laser photocoagulation effectively suppresses choroidal neovascularization (CNV) leakage and neovascularization, achieving results comparable to those with AF564 [2].