Cox, Oakley B.; Krojer, Tobias; Collins, Patrick; Monteiro, Octovia; Talon, Romain; Bradley, Anthony; Fedorov, Oleg; Amin, Jahangir; Marsden, Brian D.; Spencer, John; von Delft, Frank; Brennan, Paul E. published an article in 2016, the title of the article was A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain.Quality Control of 2-Aminomalononitrile 4-methylbenzenesulfonate And the article contains the following content:
Research into the chem. biol. of bromodomains has been driven by the development of acetyl-lysine mimetics. The ligands are typically anchored by binding to a highly conserved asparagine residue. Atypical bromodomains, for which the asparagine is mutated, have thus far proven elusive targets, including PHIP(2) whose parent protein, PHIP, has been linked to disease progression in diabetes and cancers. The PHIP(2) binding site contains a threonine in place of asparagine, and solution screening have yielded no convincing hits. We have overcome this hurdle by combining the sensitivity of X-ray crystallog., used as the primary fragment screen, with a strategy for rapid follow-up synthesis using a chem.-poised fragment library, which allows hits to be readily modified by parallel chem. both peripherally and in the core. Our approach yielded the first reported hit compounds of PHIP(2) with measurable IC50 values by an AlphaScreen competition assay. The follow-up libraries of four poised fragment hits improved potency into the sub-mM range while showing good ligand efficiency and detailed structural data. The experimental process involved the reaction of 2-Aminomalononitrile 4-methylbenzenesulfonate(cas: 5098-14-6).Quality Control of 2-Aminomalononitrile 4-methylbenzenesulfonate
The Article related to poised fragment library phip inhibitor bromodomain crystal structure, Placeholder for records without volume info and other aspects.Quality Control of 2-Aminomalononitrile 4-methylbenzenesulfonate
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts