80277-87-8Relevant academic research and scientific papers
Low molecular weight amidoximes that act as potent inhibitors of lysine-specific demethylase 1
Hazeldine, Stuart,Pachaiyappan, Boobalan,Steinbergs, Nora,Nowotarski, Shannon,Hanson, Allison S.,Casero, Robert A.,Woster, Patrick M.
, p. 7378 - 7391 (2012/10/29)
The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides, and their urea- and thiourea isosteres are potent inhibitors of LSD1 and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1 but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD), and the transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents.
3,4-Disubstituted isothiazoles: Novel potent inhibitors of VEGF receptors 1 and 2
Kiselyov, Alexander S.,Semenova, Marina,Semenov, Victor V.
scheme or table, p. 1195 - 1198 (2009/08/07)
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 × 10-5 cm/min) across Caco-2 cell monolayer.
