Vascular targeting agents for the treatment of cancers are designed to cause a rapid and selective shutdown of the blood vessels and tumors. Our previous study indicated a serial diarylisoxazole derivatives (TYC compounds) related to CA-4 composed strong anti-cancer and anti-angiogenesis activity. Utilizing protein modeling simulation analysis, TYC compounds were found to be docked into Pim-1 active site and spatially overlapped with each other. Pim-1 is an oncogene-encoded serine/threonine kinase which is associated with multiple cellular functions such as proliferation, survival, differentiation, apoptosis, and tumorigenesis. Among these TYC compounds, TYC84 showed highest consensus scoring as compared with others. Fourteen positions were found within the binding site. In 3D structure of Pim-1, TYC84 docked into the active site of Pim-1 in the same pocket as LY294002, a PI3 kinase inhibitor, resulted in inhibition of Pim-1 kinase activity. The structure of TYC84 forms hydrogen-bonds with Ser-46 and establishes 3 non-polar contacts with residues Gly-45, Ile-104, and Ile-185. Association of Pim-1 and MDM2 has been reported to induce tumorigenesis. Therefore, immunoblotting assay was used and confirmed the effect of TYC compounds on reduction of Pim-1 and MDM2 protein expression. The outcome of these results should lead to provide information to design chemical modification estimation of novel and improved compounds for anticancer therapy.