PROTACs: New method to degrade transcription regulating proteins

Hu, Bei-Chen; Zhou, Yirong; Sun, Dejuan; Yang, Yueying; Liu, Yang; Li, Xingzhou; Li, Hua; Chen, Lixia

doi:10.1016/j.ejmech.2020.112698

Cited by 34 publications

(24 citation statements)

References 106 publications

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“…To date over forty target proteins have been specifically degraded by PROTACs. Recent data have demonstrated great potential of PROTACs to target “difficult-to-target” proteins, including TFs and transcription regulating proteins, such as nuclear receptors and Bromodomain and ExtraTerminal (BET) proteins [ 98 , 99 ].…”

Section: Targeting Ap-1 Tfs For MM Therapymentioning

confidence: 99%

The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

Fan

Podar

2021

Cancers

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Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.

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Section: Targeting Ap-1 Tfs For MM Therapymentioning

confidence: 99%

The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

Fan

Podar

2021

Cancers

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“…Proteolysis targeting chimera (PROTAC) was first reported by the Crews and Deshaies laboratories in 2001 ( Hu et al, 2020 ; Pettersson et al, 2019 ). Rather than acting as conventional inhibitors, PROTACs induce selective intracellular proteolysis of target proteins.…”

Section: Other Small Molecule-based Therapeutic Modalitiesmentioning

confidence: 99%

Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review

Zheng

Zhang

et al. 2022

Front. Chem.

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Targeted therapy is a groundbreaking innovation for cancer treatment. Among the receptor tyrosine kinases, the fibroblast growth factor receptors (FGFRs) garnered substantial attention as promising therapeutic targets due to their fundamental biological functions and frequently observed abnormality in tumors. In the past 2 decades, several generations of FGFR kinase inhibitors have been developed. This review starts by introducing the biological basis of FGF/FGFR signaling. It then gives a detailed description of different types of small-molecule FGFR inhibitors according to modes of action, followed by a systematic overview of small-molecule-based therapies of different modalities. It ends with our perspectives for the development of novel FGFR inhibitors.

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“…Although PROTACs have been extensively reviewed, most of these articles have focused on the general introduction of PROTAC technology, 16,17,20,[24][25][26][27] the application of PROTACs to a specific therapeutic area [28][29][30] or a specific class of targets. 31,32 However, a comprehensive review summarizing and analysing state-of-the-art methods and strategies in the design of PROTACs is lacking. To improve the discovery efficiency and drug-likeness of future PROTACs, this review focuses on the design strategies and representative case studies of conventional and emerging types of PROTACs.…”

Section: Introductionmentioning

confidence: 99%

“…Although PROTACs have been extensively reviewed, most of these articles have focused on the general introduction of PROTAC technology, 16,17,20,24–27 the application of PROTACs to a specific therapeutic area 28–30 or a specific class of targets 31,32 . However, a comprehensive review summarizing and analysing state‐of‐the‐art methods and strategies in the design of PROTACs is lacking.…”

Section: Introductionmentioning

confidence: 99%

Strategies for designing proteolysis targeting chimaeras (PROTACs)

Dong

Cheng

et al. 2022

Medicinal Research Reviews

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Proteolysis targeting chimaeras (PROTACs) is a cutting edge and rapidly growing technique for new drug discovery and development. Currently, the largest challenge in the molecular design and drug development of PROTACs is efficient identification of potent and drug-like degraders. This review aims to comprehensively summarize and analyse state-ofthe-art methods and strategies in the design of PROTACs.We provide a detailed illustration of the general principles and tactics for designing potent PROTACs, highlight representative case studies, and discuss the advantages and limitations of these strategies. Particularly, structure-based rational PROTAC design and emerging new types of PROTACs (e.g., homo-PROTACs, multitargeting PROTACs, photo-control PROTACs and PROTAC-based conjugates) will be focused on.

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PROTACs: New method to degrade transcription regulating proteins

Cited by 34 publications

References 106 publications

The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology

Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review

Strategies for designing proteolysis targeting chimaeras (PROTACs)

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