C19-9

In this study, we identified a novel non-RGD small mol. inhibitor against the integrin αvβ3. Via virtual screening, surface plasmon resonance (SPR) assay-based affinity assay, and antitumor activity evaluation, C19 was identified as a hit compound with good affinity.In an effort to improve the anti-tumor activity of C19, several modifications were made, which led to the discovery of C19-9.Mol. dynamics (MD) simulations were conducted to search for the stable complex structure of C19-9 with integrin avβ3.C19-9 demonstrated robust anti-tumor activity in vivo and displayed good safety and stability.In conclusion, we identified C19-9, a novel non-RGD inhibitor of αvβ3 with excellent drug-like characteristics that could overcome enzalutamide-resistance in CRPC via inhibiting EMT and angiogenesis, blocking PI3K/Akt/AR and EKR signaling pathways, and improving the immunosuppressive microenvironment by JAK/STAT3/IDO signaling pathway.