3,4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2
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Updated: Jun 26, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Alexander S Kiselyov1, Marina Semenova, Victor V Semenov
1deCODE, 2501 Davey Road, Woodridge, IL 60616, USA. akiselyov@decode.com
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.
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