KRN 633 is a cell-permeable, reversible, ATP-competitive VEGFR kinase inhibitor with IC50 of 170 nM, 160 nM, and 125 nM for VEGFR-1, VEGFR-2, VEGFR-3, respectively. It inhibits PDGFR-α and c-Kit at higher concentrations only (IC50 = 0.97 µM and 4.33 µM, respectively) and inactive towards 17 other kinases (IC50 ≥ 10 µM). Shown to suppress VEGF-dependent, but not FGF-dependent, cellular signaling and cell proliferation. Although not cytotoxic to cancer cells, KRN633 exhibits excellent in vivo antitumor activity due to its inhibitory effects on vessel formation and vascular permeability.
|Cell lines||A549, Ls174T, DU145, HT29, LNCap and PC-3 cell lines|
|Preparation method||Plating cancer cells in media containig 10% FBS and antibiotics, at densities known to permit exponential growth over the assay period. Culturing the cells for 24 hours before adding KRN633 (0.01 to 10 μM) or just the vehicle (0.1% DMSO in medium) and then growing for a further 96 hours. Using WST-1 reagent to measure cell viability .|
|Concentrations||Dissolved in DMSO, final concentrations 0.01 to 10 μM|
|Incubation time||96 hours|
|Animal models||A549, Ls174T, HT29, DU145, LNCap, PC-3 cells and LC-6-JCK are established in athymic mice (BALB/cA, Jcl-nu) and athymic rats (F344/N, Jcl-rnu), respectively.|
|Formulation||Suspended in vehicle (0.5% methylcellulose solution)|
|Administration||Gavage once daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Related VEGFR/PDGFR Products|
Sunitinib is a multi-targeted RTK inhibitor targeting VEGFR2 (Flk-1) and PDGFRβ with IC50 of 80 nM and 2 nM, and also inhibits c-Kit.
Avapritinib (BLU-285) is a small molecule kinase inhibitor that potently inhibits PDGFRα D842V mutant activity in vitro (IC50 = 0.5 nM) and PDGFRα D842V autophosphorylation in the cellular setting (IC50 = 30 nM); also a potent inhibitor of the analogous KIT mutation, D816V in KIT Exon 17 (IC50 = 0.5 nM).
|Nintedanib Ethanesulfonate Salt
BIBF 1120 esylate is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.
Regorafenib (BAY 73-4506) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.
|Pazopanib HCl (GW786034 )
Pazopanib HCl (GW786034 HCl) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM in cell-free assays, respectively.
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