Strengthening Molecular Glues: Design Strategies for Improving Thalidomide Analogs as Cereblon Effectors and Anticancer Agents

Research output: Contribution to journalReview articlepeer-review

Abstract

In the two decades since a novel thalidomide analog was last approved, many promising drug candidates have emerged with remarkable potency as targeted protein degraders. Likewise, the advent of PROTACs for suppressing ‘undruggable’ protein targets reinforces the need for new analogs with improved cereblon affinity, target selectivity and drug-like properties. However, thalidomide and its approved derivatives remain plagued by several shortcomings, such as structural instability and poor solubility. Herein, we present a review of strategies for mitigating these shortcomings and highlight contemporary drug discovery approaches that have generated novel thalidomide analogs with enhanced efficacy as cereblon effectors and/or anticancer agents.

Original languageEnglish
Article number104010
Number of pages11
JournalDrug Discovery Today
Volume29
Issue number6
DOIs
Publication statusPublished - Jun 2024

Fingerprint

Dive into the research topics of 'Strengthening Molecular Glues: Design Strategies for Improving Thalidomide Analogs as Cereblon Effectors and Anticancer Agents'. Together they form a unique fingerprint.

Cite this