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- W4296312353 endingPage "4492" @default.
- W4296312353 startingPage "4492" @default.
- W4296312353 abstract "Multiple myeloma (MM) is the second most common hematological malignancy with a recurrent clinical course. The introduction of immunomodulatory drugs (IMiDs) was one of the milestones in MM therapy leading to a significant improvement in patients' prognosis. Currently, IMiDs are the backbone of MM therapy in newly diagnosed and relapsed/refractory settings. It is now known that IMiDs exert their anti-myeloma activity mainly by binding cereblon (CRBN), the substrate receptor protein of the CRL4 E3 ubiquitin ligase (CRL4CRBN) complex. By binding CRBN, IMiDs alter its substrate specificity, leading to ubiquitination and proteasomal degradation of proteins essential for MM cell survival. Following the success of IMiDs, it is not surprising that the possibility of using the CRL4CRBN complex's activity to treat MM is being further explored. In this review, we summarize the current state of knowledge about novel players in the MM therapeutic landscape, namely the CRBN E3 ligase modulators (CELMoDs), the next generation of IMiDs with broader biological activity. In addition, we discuss a new strategy of tailored proteolysis called proteolysis targeting chimeras (PROTACs) using the CRL4CRBN to degrade typically undruggable proteins, which may have relevance for the treatment of MM and other malignancies in the future." @default.
- W4296312353 created "2022-09-20" @default.
- W4296312353 creator A5017433276 @default.
- W4296312353 creator A5022628384 @default.
- W4296312353 creator A5025023747 @default.
- W4296312353 creator A5086914724 @default.
- W4296312353 date "2022-09-16" @default.
- W4296312353 modified "2023-10-17" @default.
- W4296312353 title "CRL4CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma" @default.
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