Ladds, Marcus J. G. W. published the artcileExploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: a case study in polypharmacology, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is Journal of Biological Chemistry (2020), 295(52), 17935-17949, database is CAplus and MEDLINE.
The tenovins are a frequently studied class of compounds capable of inhibiting sirtuin activity, which is thought to result in increased acetylation and protection of the tumor suppressor p53 from degradation However, as we and other laboratories have shown previously, certain tenovins are also capable of inhibiting autophagic flux, demonstrating the ability of these compounds to engage with more than one target. In this study, we present two addnl. mechanisms by which tenovins are able to activate p53 and kill tumor cells in culture. These mechanisms are the inhibition of a key enzyme of the de novo pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH), and the blockage of uridine transport into cells. These findings hold a 3-fold significance: first, we demonstrate that tenovins, and perhaps other compounds that activate p53, may activate p53 by more than one mechanism; second, that work previously conducted with certain tenovins as SirT1 inhibitors should addnl. be viewed through the lens of DHODH inhibition as this is a major contributor to the mechanism of action of the most widely used tenovins; and finally, that small changes in the structure of a small mol. can lead to a dramatic change in the target profile of the mol. even when the phenotypic readout remains static.
Journal of Biological Chemistry published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.
Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics