In vitro
KRN633 can inhibit tyrosine phosphorylation of VEGFR-2 with IC50 of 1.16 nM in human umbilical vein endothelial cells.KRN633 is highly selective for VEGFR-1, VEGFR-2, and VEGFR-3. KRN633 also can block the activation of mitogen-activated protein kinases by VEGF, along with human umbilical vein endothelial cell proliferation and tube formation. The propagation of various cancer cell lines in vitro was not inhibited by KRN633. KRN633 also shows suppression on HIF-1alpha accumulation under the hypoxic condition. The VEGFR tyrosine kinase inhibitors, KRN633, possess dual functions:inhibition of VEGFR signaling and HIF-1alpha expression under the hypoxic condition. KRN633 suppresses HIF-1alpha expression through inhibition of both Akt and ERK phosphorylation signaling pathways. Administration of KRN633 can decreases the alkaline phosphatase (ALP) activity during the osteoblastic differentiation of cultured human periosteal-derived cells.
Download Datasheet