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Overview
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Background
KRN 633 is a selective inhibitor of VEGFR-1, VEGFR-2 and VEGFR-3 with IC50 value of 170 nM, 160 nM and 125 nM [1].Vascular endothelial growth factor receptor (VEGFR) is a protein and plays an important role in tumor angiogenesis by cooperating with its ligand VEGF [1].KRN 633 is a potent VEGFR inhibitor. When tested with HUVECs, KRN 633 inhibited the cell proliferation that mediated by VEGF with the IC50 value of 14.9 nmol/L and suppressed the capillary tube formation by ~50% at the dose of 10 nmol/L [1].In mid-pregnant mice model, KRN633 was used at the dose of 5 mg/kg once daily from embryonic day 13.5 until the day of delivery and the effect on vascular growth was slightly delayed on postnatal day 4 (P4) and on P8 it was observed that KRN633 resulted in the decreased numbers of central arteries and veins and abnormal branching of the central arteries [2]. When tested with athymic mouse xenograft HT29 cells model, administration of KRN633 inhibited tumor growth as ~90% from the initial tumor volume rangs from 500-667 mm3, while had less effect Du145 xenograft mouse models by inhibiting tumor angiogenesis and vascular permeability [1].
[1]. Nakamura, K., et al., KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth. Mol Cancer Ther, 2004. 3(12): p. 1639-49.
[2]. Morita, A., et al., Treatment of mid-pregnant mice with KRN633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces abnormal retinal vascular patterning in their newborn pups. Birth Defects Res B Dev Reprod Toxicol, 2014. 101(4): p. 293-9.
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