334022-78-5Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)
Korwar, Sudha,Morris, Benjamin L.,Parikh, Hardik I.,Coover, Robert A.,Doughty, Tyler W.,Love, Ian M.,Hilbert, Brendan J.,Royer, William E.,Kellogg, Glen E.,Grossman, Steven R.,Ellis, Keith C.
, p. 2707 - 2715 (2016/06/08)
C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD+ as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 μM) and 3-chloro- (IC50 = 0.17 μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer.
Chemocontrolled reduction of aromatic α-ketoesters by NaBH4: Selective synthesis of α-hydroxy esters or 1,2-diols
Dalla, Vincent,Cotelle, Philippe,Catteau, Jean Pierre
, p. 1577 - 1580 (2007/10/03)
α-Hydroxyesters 5a-g or diols 6a-g have been obtained in high yields by reduction of aromatic α-ketoesters 4 once or twice respectively by using NaBH4 as the reducer under suitable conditions. The use of a solvent that does not interact with the reagent allowed the double reduction to occur with only a slight excess of borohydride in very mild conditions.
