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• W4313592920 startingPage "141" @default.
• W4313592920 abstract "Thalidomide and its analogues are frequently used in PROTAC design. However, they are known to be inherently unstable, undergoing hydrolysis even in commonly utilized cell culture media. We recently reported that phenyl glutarimide (PG)-based PROTACs displayed improved chemical stability and, consequently, improved protein degradation efficacy and cellular potency. Our optimization efforts, aiming to further improve the chemical stability and eliminate the racemization-prone chiral center in PG, led us to the development of phenyl dihydrouracil (PD)-based PROTACs. Here we describe the design and synthesis of LCK-directing PD-PROTACs and compare their physicochemical and pharmacological properties to those of the corresponding IMiD and PG analogues." @default.
• W4313592920 created "2023-01-06" @default.
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• W4313592920 date "2023-01-04" @default.
• W4313592920 modified "2023-10-18" @default.
• W4313592920 title "Phenyl Dihydrouracil: An Alternative Cereblon Binder for PROTAC Design" @default.
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• W4313592920 doi "https://doi.org/10.1021/acsmedchemlett.2c00436" @default.
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