Baud, Matthias G. J. published the artcileAminobenzothiazole derivatives stabilize the thermolabile p53 cancer mutant Y220C and show anticancer activity in p53-Y220C cell lines, Category: alcohols-buliding-blocks, the publication is European Journal of Medicinal Chemistry (2018), 101-114, database is CAplus and MEDLINE.
Many cancers have the tumor suppressor p53 inactivated by mutation, making reactivation of mutant p53 with small mols. a promising strategy for the development of novel anticancer therapeutics. The oncogenic p53 mutation Y220C, which accounts for approx. 100,000 cancer cases per yr, creates an extended surface crevice in the DNA-binding domain, which destabilizes p53 and causes denaturation and aggregation. Here, we describe the structure-guided design of a novel class of small-mol. Y220C stabilizers and the challenging synthetic routes developed in the process. The synthesized chem. probe MB710, an aminobenzothiazole derivative, binds tightly to the Y220C pocket and stabilizes p53-Y220C in vitro. MB725, an ethylamide analog of MB710, induced selective viability reduction in several p53-Y220C cancer cell lines while being well tolerated in control cell lines. Reduction of viability correlated with increased and selective transcription of p53 target genes such as BTG2, p21, PUMA, FAS, TNF, and TNFRSF10B, which promote apoptosis and cell cycle arrest, suggesting compound-mediated transcriptional activation of the Y220C mutant. Our data provide a framework for the development of a class of potent, non-toxic compounds for reactivating the Y220C mutant in anticancer therapy.
European Journal of Medicinal Chemistry published new progress about 2240-88-2. 2240-88-2 belongs to alcohols-buliding-blocks, auxiliary class Trifluoromethyl,Fluoride,Aliphatic hydrocarbon chain,Alcohol, name is 3,3,3-Trifluoropropan-1-ol, and the molecular formula is C3H5F3O, Category: alcohols-buliding-blocks.
Referemce:
https://en.wikipedia.org/wiki/Alcohol,
Alcohols – Chemistry LibreTexts