5852-78-8Relevant academic research and scientific papers
Enzyme-like catalysis by single chain nanoparticles that use transition metal cofactors
Alzona, Ariale J.,Chen, Junfeng,Garcia, Edzna S.,Xiong, Thao M.,Zhu, Lingyang,Zimmerman, Steven C.
supporting information, p. 985 - 988 (2022/01/28)
We report a modular approach in which a noncovalently cross-linked single chain nanoparticle (SCNP) selectively binds catalyst cofactors and substrates to increase both the catalytic activity of a Cu-catalyzed alkyne-azide cycloaddition reaction and the Ru-catalyzed cleavage of allylcarbamate groups compared to the free catalysts. This journal is
BRIDGED BICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
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Paragraph 1303-1304, (2019/05/15)
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor
A cell-permeable ester derivative of the JmjC histone demethylase inhibitor IOX1
Schiller, Rachel,Scozzafava, Giuseppe,Tumber, Anthony,Wickens, James R.,Bush, Jacob T.,Rai, Ganesha,Lejeune, Clarisse,Choi, Hwanho,Yeh, Tzu-Lan,Chan, Mun Chiang,Mott, Bryan T.,McCullagh, James S. O.,Maloney, David J.,Schofield, Christopher J.,Kawamura, Akane
supporting information, p. 566 - 571 (2014/03/21)
The 2-oxoglutarate (2OG)-dependent Jumonjia C domain (JmjC) family is the largest family of histone lysine demethylases. There is interest in developing small-molecule probes that modulate JmjC activity to investigate their biological roles. 5-Carboxy-8-hydroxyquinoline (IOX1) is the most potent broad-spectrum inhibitor of 2OG oxygenases, including the JmjC demethylases, reported to date; however, it suffers from low cell permeability. Here, we describe structure-activity relationship studies leading to the discovery of an n-octyl ester form of IOX1 with improved cellular potency (EC50 value of 100 to 4a μM). These findings are supported by in vitro inhibition and selectivity studies, docking studies, activity versus toxicity analysis in cell cultures, and intracellular uptake measurements. The n-octyl ester was found to have improved cell permeability; it was found to inhibit some JmjC demethylases in its intact ester form and to be more selective than IOX1. The n-octyl ester of IOX1 should find utility as a starting point for the development of JmjC inhibitors and as a use as a cell-permeable tool compound for studies investigating the roles of 2OG oxygenases in epigenetic regulation.
Development of new cathepsin b inhibitors: Combining bioisosteric replacements and structure-based design to explore the structure-activity relationships of nitroxoline derivatives
Sosi?, Izidor,Mirkovi?, Bojana,Arenz, Katharina,?tefane, Bogdan,Kos, Janko,Gobec, Stanislav
supporting information, p. 521 - 533 (2013/04/24)
Human cathepsin B has many house-keeping functions, such as protein turnover in lysosomes. However, dysregulation of its activity is associated with numerous diseases, including cancers. We present here the structure-based design and synthesis of new cathepsin B inhibitors using the cocrystal structure of 5-nitro-8-hydroxyquinoline in the cathepsin B active site. A focused library of over 50 compounds was prepared by modifying positions 5, 7, and 8 of the parent compound nitroxoline. The kinetic parameters and modes of inhibition were characterized, and the selectivities of the most promising inhibitors were determined. The best performing inhibitor 17 was effective in cell-based in vitro models of tumor invasion, where it significantly abrogated invasion of MCF-10A neoT cells. These data show that we have successfully explored the structure-activity relationships of nitroxoline derivatives to provide new inhibitors that could eventually lead to compounds with clinical usefulness against the deleterious effects of cathepsin B in cancer progression.
