Inducing or enhancing protein-protein interaction to develop drugs: Molecular glues with various biological activity
Rongyu Zhang1, Yirong Zheng1, Fengjiao Xiang1
1Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua, 321004, PR China.
Abstract:
Over the past two decades, molecular glues (MGs) have gradually attracted the attention of the pharmaceutical community with the advent of MG degraders such as IMiDs and indisulam. Such molecules degrade the target protein by promoting the interaction between the target protein and E3 ligase. In addition, as a chemical inducer, MGs promote the dimerization of homologous proteins and heterologous proteins to form ternary complexes, which have great prospects in regulating biological activities. This review focuses on the application of MGs in the field of drug development including protein-protein interaction (PPI) stability and protein degradation. We thoroughly analyze the structure of various MGs and the interactions between MGs and various biologically active molecules, thus providing new perspectives for the development of PPI stabilizers and new degraders.
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