Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src

Manda, Sudhakar; Lee, Na Keum; Oh, Dong‐Chan; Lee, Jeeyeon

doi:10.3390/molecules25081948

Cited by 17 publications

(15 citation statements)

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“…Promoting apoptosis is one of the main methods to treat tumors. However, the anti-apoptotic properties may lead to resistance to cytotoxic chemotherapeutic drugs or radiotherapy [ 106 ]. Necroptosis is another type of regulated cell death closely related to the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) and mixed-lineage kinase domain-like protein (MLKL) [ 107 ].…”

Section: Ru(ii) Complexesmentioning

confidence: 99%

Ruthenium Complexes as Promising Candidates against Lung Cancer

Sun

Shi

et al. 2021

Molecules

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Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.

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Section: Ru(ii) Complexesmentioning

confidence: 99%

Ruthenium Complexes as Promising Candidates against Lung Cancer

Sun

Shi

et al. 2021

Molecules

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“…Tumor-suppressor proteins are indicated in blue and oncogenic proteins are indicated in red. In the presented pathways, PROTACs have been developed targeting FAK [ 246 , 247 ], IGF-1R [ 248 ], p38 [ 249 , 250 ], Smad3 [ 251 ], Src [ 248 , 252 ], TCF [ 253 ], TGF-β1 [ 254 ] and β-catenin [ 255 ] …”

Section: Protacs In Targeted Cancer Therapymentioning

confidence: 99%

Proteolysis-targeting chimeras (PROTACs) in cancer therapy

Zheng

et al. 2022

Mol Cancer

121

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Proteolysis-targeting chimeras (PROTACs) are engineered techniques for targeted protein degradation. A bifunctional PROTAC molecule with two covalently-linked ligands recruits target protein and E3 ubiquitin ligase together to trigger proteasomal degradation of target protein by the ubiquitin-proteasome system. PROTAC has emerged as a promising approach for targeted therapy in various diseases, particularly in cancers. In this review, we introduce the principle and development of PROTAC technology, as well as the advantages of PROTACs over traditional anti-cancer therapies. Moreover, we summarize the application of PROTACs in targeting critical oncoproteins, provide the guidelines for the molecular design of PROTACs and discuss the challenges in the targeted degradation by PROTACs.

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“…In 2020, Lee group designed a variety of degraders based on different types of IGF-1R inhibitors and CRBN. 86 The ligands for the targeted protein included IGF-1R/Src dual-target inhibitors. During the screening process, it was found that the degraders 42 ( CPR3 , Fig.…”

Section: Protacs Targeting Cancer-related Targetsmentioning

confidence: 99%

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

Cao

et al. 2022

Sig Transduct Target Ther

112

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PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin–proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article “PROTACs: great opportunities for academia and industry” in the journal, summarizing the representative compounds of PROTACs reported before the end of 2019. In the past 2 years, the entire field of protein degradation has experienced rapid development, including not only a large increase in the number of research papers on protein-degradation technology but also a rapid increase in the number of small-molecule degraders that have entered the clinical and will enter the clinical stage. In addition to PROTAC and molecular glue technology, other new degradation technologies are also developing rapidly. In this article, we mainly summarize and review the representative PROTACs of related targets published in 2020–2021 to present to researchers the exciting developments in the field of protein degradation. The problems that need to be solved in this field will also be briefly introduced.

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Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src

Cited by 17 publications

References 50 publications

Ruthenium Complexes as Promising Candidates against Lung Cancer

Ruthenium Complexes as Promising Candidates against Lung Cancer

Proteolysis-targeting chimeras (PROTACs) in cancer therapy

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

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