Targeting the undruggables—the power of protein degraders

Zhang, Chao; Liu, Yongbo; Li, Guangchen; Yang, Zhouli; Han, Chi; Sun, Xiuyun; Sheng, Chunquan; Ding, Ke; Rao, Yu

doi:10.1016/j.scib.2024.03.056

Cited by 13 publications

(1 citation statement)

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“…The field of TPD offers a versatile platform for identifying and selectively degrading disease-causing proteins, including previously “undruggable” targets (STAT3, KRAS G12C , and CDK2) . This opens new possibilities for combination therapies with immunotherapy, as novel targets can be used further to strengthen the immune response to cancer cells …”

Section: Why Such An Interest In Immunology?mentioning

confidence: 99%

Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions

Kamaraj,

Ghosh,

Das

et al. 2024

Bioconjugate Chem.

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Targeted protein degradation or TPD, is rapidly emerging as a treatment that utilizes small molecules to degrade proteins that cause diseases. TPD allows for the selective removal of disease-causing proteins, including proteasome-mediated degradation, lysosome-mediated degradation, and autophagy-mediated degradation. This approach has shown great promise in preclinical studies and is now being translated to treat numerous diseases, including neurodegenerative diseases, infectious diseases, and cancer. This review discusses the latest advances in TPD and its potential as a new chemical modality for immunotherapy, with a special focus on the innovative applications and cutting-edge research of PROTACs (Proteolysis TArgeting Chimeras) and their efficient translation from scientific discovery to technological achievements. Our review also addresses the significant obstacles and potential prospects in this domain, while also offering insights into the future of TPD for immunotherapeutic applications.

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Section: Why Such An Interest In Immunology?mentioning

confidence: 99%