Therefore, Hsp60 is a novel regulator of mitochondrial permeability transition, contributing to a cytoprotective chaperone network that antagonizes CypD-dependent cell death in tumors. Cancer Res; 70(22); 8988-93.
(C) 2010 AACR.”
“Cytidine deaminase (EC 220.127.116.11, CDA), an enzyme of the pyrimidine salvage pathways, is responsible for the degradation and inactivation of several cytidine-based antitumor drugs such as cytarabine, gemcitabine, decitabine, and check details azacytidine. Thus, CDA inhibitors are highly sought after as compounds to be co-administered with said drugs to improve their effectiveness. Alternatively, the design of antitumor drugs not susceptible to the action of CDA is also regarded as an attractive solution. Herein we describe a virtual screen for CDA ligands based on chemical Sotrastaurin similarity and molecular docking. The campaign led to the identification of three novel inhibitors and one novel substrate, with a 19% hit rate, and allowed a significant extension of the structure-activity relationships, also in light of the compounds that resulted inactive. The most active compound identified through the screen is the inhibitor pseudoisocytidine, which has the potential to serve as a lead for highly stable compounds. The study also delineated the detrimental effect of 5-aza and 6-aza
substitutions, the incompatibility of the presence of an amino group at the 3′-position, as well as the presence of very strict steric requirements around the 2′-arabino position and, even more, the N4-position. Importantly, https://www.selleckchem.com/products/ly2090314.html these features can be exploited for the design of novel antineoplastic agents resistant to the action of CDA.”
“White matter lesions, commonly seen on, MRIs of elderly people, are related to various geriatric disorders, including cerebrovascular diseases, cardiovascular diseases, dementia, and psychiatric disorders. Currently, white matter lesions are divided into periventricular
white matter lesions and deep white matter lesions. Although the meaning of these terms varies by study and this dichotomization itself is still in debate, a possible dissimilarity in pathogenic mechanisms between periventricular white matter lesions and deep white matter lesions are providing some clues for understanding pathophysiology of many geriatric syndromes associated with white matter lesions. We have reviewed the distinctions between periventricular white matter lesions and deep white matter lesions in terms of etiology, histopathology, functional correlates, and imaging methodologies. We suggest a new subclassification of white matter lesions that might have better etiological and functional relevance than the current simple dichotomization. The new categories are juxtaventricular, periventricular, deep white, and juxtacortical. This new classification scheme might contribute to reducing the heterogeneity of white matter lesion findings in future research.