3,4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2.
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Kiselyov AS, Semenova M, Semenov VV
3,4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2.
Bioorg Med Chem Lett. 2009 Feb 15;19(4):1195-8. doi: 10.1016/j.bmcl.2008.12.078. Epub 2008 Dec 24.
- PubMed ID
- 19124243 [ View in PubMed]
- Abstract
Novel derivatives of isothiazoles are described as potent ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds exhibited VEGFR-2 inhibitory activity comparable to that of Vatalanib in both HTRF enzymatic and cellular assays. Several derivatives featuring bulky meta-substituents in the amide portion of the molecule displayed 4- to 8-fold specificity for VEGFR-2 versus VEGFR-1. Active molecules also showed high intrinsic permeability (> 30 x 10(-5) cm/min) across Caco-2 cell monolayer.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Vatalanib Vascular endothelial growth factor receptor 1 IC 50 (nM) 140 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 1 IC 50 (nM) 110 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 54 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 21 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 42 N/A N/A Details Vatalanib Vascular endothelial growth factor receptor 2 IC 50 (nM) 16 N/A N/A Details