Krabill, Aaron D.; Chen, Hao; Hussain, Sajjad; Hewitt, Chad S.; Imhoff, Ryan D.; Muli, Christine S.; Das, Chittaranjan; Galardy, Paul J.; Wendt, Michael K.; Flaherty, Daniel P. published an article in 2021, the title of the article was Optimization and anti-cancer properties of fluoromethylketones as covalent inhibitors for ubiquitin C-terminal hydrolase L1.Category: esters-buliding-blocks And the article contains the following content:
The deubiquitinating enzyme (DUB) UCHL1 is implicated in various disease states including neurodegenerative disease and cancer. However, there is a lack of quality probe mols. to gain a better understanding on UCHL1 biol. To this end a study was carried out to fully characterize and optimize the irreversible covalent UCHL1 inhibitor VAEFMK. Structure-activity relationship studies identified modifications to improve activity vs. the target and a full cellular characterization was carried out for the first time with this scaffold. The studies produced a new inhibitor, 34, with an IC50 value of 7.7 μM against UCHL1 and no observable activity vs. the closest related DUB UCHL3. The mol. was also capable of selectively inhibiting UCHL1 in cells and did not demonstrate any discernible off-target toxicity. Finally, the mol. was used for initial probe studies to assess the role of UCHL1 role in proliferation of myeloma cells and migration behavior in small cell lung cancer cells making 34 a new tool to be used in the biol. evaluation of UCHL1. The experimental process involved the reaction of (S)-5-tert-Butyl 1-methyl 2-aminopentanedioate(cas: 53838-27-0).Category: esters-buliding-blocks
The Article related to uchl fluoromethylketone covalent inhibitor optimization anticancer property, uchl1 inhibitors, covalent inhibitors, deubiquitinases, fluoromethylketones, Placeholder for records without volume info and other aspects.Category: esters-buliding-blocks
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