ATN-161 (trifluoroacetate salt)

ATN-161 trifluoroacetate salt is a novel integrin α5β1 antagonist, which inhibits angiogenesis and growth of liver metastases in a murine model. IC50 & Target: Integrin α5β1^[1] In Vitro: The combination of ATN-161 plus 5-FU significantly reduces tumor cell proliferation compared to control and single-agent therapy (p<0.01). In addition, combination therapy leads to a significant increase of apoptotic (TUNEL-positive) tumor cells (p<0.03), whereas single-agent therapy does not increase in TUNEL-positive tumor cells. ATN-161 treatment leads to a significant reduction in EC number (21% decrease) after a 48 hr incubation time compared to control (p<0.03)^[1]. ATN-161 inhibites VEGF-induced migration and capillary tube formation in hCECs, but did not inhibit proliferation. ATN-161 decreases the number of cells migrating in response to VEGF in a dose-dependent manner starting at 100 nM (P<0.001 vs. VEGF group)^[2]. In Vivo: The preliminary experiments with α5β1-negative human colon cancer xenografts (HT29) show that treatment with ATN-161 significantly reduces tumor weight and vessel density^[1]. Injection of ATN-161 after laser photocoagulation inhibits choroidal neovascularization (CNV) leakage and neovascularization to an extent similar to AF564^[2].