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TARGETED PROTEIN DEGRADATION USING A MUTANT E3 UBIQUITIN LIGASE

机译:使用突变E3泛素连接酶进行目标蛋白降解

摘要

The present application provides bifunctional compounds of Formula I or II: or an enantiomer, diastereomer, or stereoisomer, or a pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds of Formula (I) or (II) that link a mutant cereblon-binding moiety to a ligand that is capable of binding to a targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof. The present application also relates to polynucleotides or polypeptides of a mutant cereblon and methods of use thereof.
机译:本申请提供式I或II的双官能化合物:或其对映异构体,非对映异构体或立体异构体,或其药学上可接受的盐,其充当诱导蛋白质降解的部分。本申请还涉及通过使用式(I)或(II)的双功能化合物将内源蛋白质靶向降解的方法,所述化合物将突变型脑神经结合部分与能够与靶蛋白质结合的配体连接可用于治疗增生性疾病。本申请还提供了制备本申请化合物及其中间体的方法。本申请还涉及突变型大脑的多核苷酸或多肽及其使用方法。

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