KRN-633 is an effective VEGFR inhibitor. The IC50s of KRN-633(KRN633) for VEGFR1, VEGFR2, and VEGFR3 is 170, 160 and 125 nM, respectively.

VEGFR1:170 nM, VEGFR2:160 nM, VEGFR3:125 nM

In human umbilical vein endothelial cells, KRN-633 inhibits tyrosine phosphorylation of VEGFR-1, VEGFR2, c-Kit, and PDGFR-β with IC50 of 11.7, 1.16, 8.01, 130 nM, respectively. In endothelial cells, KRN-633 inhibits the formation of the capillary tube. KRN-633 suppress the VEGF-driven proliferation of HUVECs (IC50=14.9 nM).

In athymic mouse and rat xenograft models, KRN-633 was able to inhibit tumor growth in various tissue sources such as lungs, colon, and prostate. It was also observed that in the non-necrosis region of tumor grafts, the number of endothelial cells was reduced and vascular permeability decreased. In the regenerated tumors, KRN-633 can also ablate tumor growth.

In cell-free kinase assays,with1 μM ATP the IC50 of KRN-633 is from 0.3 nM to 10 μM.

Cancer cells, such as A549, Ls174T, HT29, DU145, LNCap, and PC-3 cells, are cultured for 24 hours, then add KRN-633 (0.01 to 10 μM)that is prepared in 0.1% DMSO in the medium growing for 96 hours.

In tumor xenografts mice model, are treated with KRN-633(10-100 mg/kg) once or twice per day. In human tumor xenografts athymic rats (BALB/cA, Jcl-nu), when the tumors reach the average size indicated (162 to 657 mm3), and are treated with KRN-633 either once or twice per day. After 14days treatment, Calculate the tumor growth inhibition.