AT-533 is a potent inhibitor of Hsp90 and HSV. AT-533 blocks the HIF-1α/VEGF/VEGFR-2 signaling pathway, leading to suppress tumor growth and angiogenesis. AT-533 also inhibits the activation of the downstream pathways, including Erk1/2, FAK, Akt/mTOR/p70S6K,. AT-533 inhibits the cell migration, invasion, and the tube formation of human umbilical vein endothelial cells (HUVECs).

AT-533 (0-1350 nM; 24h or 48h) inhibits 20 ng/mL VEGF-induced tube formation, cell migration, and HUVEC invasion. Additionally, AT-533 (2 μM or 75 μM; 24h) hinders the HIF-1α/VEGF signaling pathway in hypoxia-induced breast cancer cells and inhibits Akt/mTOR/p70S6K, Erk1/2, and FAK phosphorylation. It shows anti-angiogenic activity on the chorionic villus (CAM) model at 10 nM and 50 nM over 48h. Furthermore, AT-533 (0.5 μM; 2 or 4 hours) reduces TNF-α, IL-1β, and IL-6 production induced by HSV-1 in RAW264.7 and BV2 cells [1, 2].

AT-533 (10 mg/kg; intraperitoneal injection; once daily for 21 days) inhibited the expression of HIF-1α/VEGF signaling pathway-related proteins in a mouse MDA-MB-231 xenograft model of breast cancer [1]. AT-533 (1, 2, 4 mg/kg; intraperitoneal injection; once daily for 30 days) did not cause death, appetite loss, weight loss, or adverse reactions in subacute toxicity tests of Sprague Dawley rats [3].