882500-18-7Relevant articles and documents
Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships
Leung, Leo,Niculescu-Duvaz, Dan,Smithen, Deborah,Lopes, Filipa,Callens, Cedric,McLeary, Robert,Saturno, Grazia,Davies, Lawrence,Aljarah, Mohammed,Brown, Michael,Johnson, Louise,Zambon, Alfonso,Chambers, Tim,Ménard, Delphine,Bayliss, Natasha,Knight, Ruth,Fish, Laura,Lawrence, Rae,Challinor, Mairi,Tang, Haoran,Marais, Richard,Springer, Caroline
supporting information, p. 5863 - 5884 (2019/07/04)
Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing an aminomethylenethiophene (AMT) scaffold. High-throughput screening provided the initial hits. Structure-activity relationship (SAR) studies led to the discovery of AMT inhibitors with sub-micromolar half-maximal inhibitory concentrations (IC50) in a LOX enzyme activity assay. Further SAR optimization yielded the orally bioavailable LOX inhibitor CCT365623 with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.
Bisaryl-sulfonamides
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Page/Page column 33, (2008/06/13)
Compounds, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by PPARγ or PPARδ. In particular, the compounds of the invention modulate the function of PPARγ or PPARδ. The subject methods are particularly useful in the treatment and/or prevention of diabetes, obesity, hypercholesterolemia, rheumatoid arthritis and atherosclerosis.
