Pazopanib HCl Chemical Structure
VEGFR enzyme assays for VEGGR1,VEGFR2 and VEGFR3 were running in homogeneous time-resolved fluorescence (HTRF) format in 384-well microtiter plates using a purified, baculovirus-expressed glutathione-S-transferase (GST) fusion protein encoding the catalytic c-terminus of human VEGFR receptor kinases 1, 2, or 3.
Pazopanib HCl showed good potency against all the human VEGFR receptors with an IC50 of 10, 30, and 47 nM for VEGFR-1, -2, and -3, respectively. Significant activity was also seen against the closely related tyrosine receptor kinases PDGFR beta, c-Kit, FGF-R1, and c-fms with IC50’s of 84, 74, 140,and 146 nM, respectively. In cellular assays, in addition to inhibiting the VEGF-induced proliferation of HUVECs, Pazopanib HCl potently inhibited VEGF-induced phosphorylation of VEGFR-2 in HUVEC cells with an IC50 of ∼8 nM.
The cytochrome P450 profile was also improved with inhibition >10 μM against the isozymes tested, with the exception of 2C9 (7.9 μM). 
 J. Med. Chem. 2008;51, 4632–4640
|Molecular Weight (WM):||473.98|
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