DNA Nanotechnology for Application in Targeted Protein Degradation DOI
Yang Xiao, Xinyi Guo, Weiwei Zhang

и другие.

ACS Biomaterials Science & Engineering, Год журнала: 2024, Номер 10(11), С. 6814 - 6827

Опубликована: Окт. 5, 2024

DNA is a kind of flexible and versatile biomaterial for constructing nanostructures nanodevices. Due to high biocompatibility programmability easy modification fabrication, nanotechnology has emerged as powerful tool application in intracellular targeted protein degradation. In this review, we summarize the recent advances design mechanism degradation technologies such hydrolysis chimeras, lysosomal autophagy based Subsequently, introduce nanotechnologies cascade circuits, nanostructures, dynamic machines. Moreover, present latest developments Finally, vision challenges are discussed.

Язык: Английский

Journey of PROTAC: From Bench to Clinical Trial and Beyond DOI

Kyli Berkley,

Julian Zalejski, Nidhi Sharma

и другие.

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Proteolysis-targeting chimeras (PROTACs) represent a transformative advancement in drug discovery, offering method to degrade specific intracellular proteins. Unlike traditional inhibitors, PROTACs are bifunctional molecules that target proteins for elimination, enabling the potential treatment of previously "undruggable" This concept, pioneered by Crews and his team, introduced use small link protein an E3 ubiquitin ligase, inducing ubiquitination subsequent degradation protein. By promoting rather than merely inhibiting function, present novel therapeutic strategy with enhanced specificity effectiveness, especially areas such as cancer neurodegenerative diseases. Since their initial field PROTAC research has rapidly expanded numerous now designed wide range disease-relevant The substantial research, investment, collaboration across academia pharmaceutical industry reflect growing interest PROTACs. Review discusses journey from discovery clinical trials, highlighting advancements challenges. Additionally, recent developments fluorescent photogenic PROTACs, used real-time tracking degradation, presented, showcasing evolving targeted therapy.

Язык: Английский

Процитировано

3
Glycoscience in Advancing PD-1/PD-L1-Axis-Targeted Tumor Immunotherapy DOI Open Access
Qianqian Sun, Senlian Hong

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1238 - 1238

Опубликована: Янв. 31, 2025

Immune checkpoint blockade therapy, represented by anti-PD-1/PD-L1 monoclonal antibodies, has significantly changed the immunotherapy landscape. However, treatment is still limited unsatisfactory response rates, immune-related adverse effects, and drug resistance. Current studies have established that glycosylation, a common post-translational modification, crucial in promoting cancer progression immune invasion. Targeting aberrant glycosylation cancers presents precision medicine regimens for monitoring developing personalized medicine. Notably, checkpoints PD-1 PD-L1 are highly glycosylated, which affects PD-1/PD-L1 interaction binding of antibodies. Recent achievements glycoscience to enhance patient outcomes, referred as glycotherapy, underscored their high potency advancing therapies, i.e., glycoengineered antibodies with improved toward PD-1/PD-L1, pharmaceutic inhibitors core fucosylation sialylation, synergistic antibody-sialidase conjugate. This review briefly introduces axis highlights fundamental applied advances improve immunoblockade therapies.

Язык: Английский

Процитировано

0
Unleashing the Power of Covalent Drugs for Protein Degradation DOI Open Access

Meng‐Jie Fu,

Hang Jin,

Shao‐Peng Wang

и другие.

Medicinal Research Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

ABSTRACT Targeted protein degradation (TPD) has emerged as a significant therapeutic approach for variety of diseases, including cancer. Advances in TPD techniques, such molecular glue (MG) and lysosome‐dependent strategies, have shown substantial progress since the inception first PROTAC 2001. The methodology represents forefront technology, with ongoing evaluation more than 20 clinical trials treatment diverse medical conditions. Two prominent PROTACs, ARV‐471 ARV‐110, are currently undergoing phase III II trials, respectively. Traditional PROTACs encountering obstacles limited binding affinity restricted range E3 ligase ligands facilitating interest (POI) degradation. Covalent medicines offer potential to enhance efficacy by enabling targeting previously considered “undruggable” shallow sites. Strategic alterations allow establish covalent connections particular target proteins, Kirsten rat sarcoma viral oncogene homolog (KRAS), Bruton's tyrosine kinase (BTK), epidermal growth factor receptor (EGFR), well ligases DDB1 CUL4 associated 16 (DCAF16) Kelch‐like ECH‐associated 1 (Keap1). concept also been utilized various new forms degraders, molecule (MG), in‐cell click‐formed proteolysis chimera (CLIPTAC), HaloPROTAC, lysosome‐targeting (LYTAC) GlueTAC. This review focuses on recent advancements degraders beyond examines future directions pertinent this field.

Язык: Английский

Процитировано

0
PROTACs coupled with oligonucleotides to tackle the undruggable DOI
Guangshuai Zhang,

Si Yan,

Yan Liu

и другие.

Bioanalysis, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Фев. 3, 2025

Undruggable targets account for roughly 85% of human disease-related and represent a category therapeutic that are difficult to tackle with traditional methods, but their considerable clinical importance. These generally defined by planar functional interfaces the absence efficient ligand-binding pockets, making them unattainable conventional pharmaceutical strategies. The advent oligonucleotide-based proteolysis-targeting chimeras (PROTACs) has instilled renewed optimism in addressing these challenges. PROTACs facilitate targeted degradation undruggable entities, including transcription factors (TFs) RNA-binding proteins (RBPs), via proteasome-dependent mechanisms, thereby presenting novel approaches diseases linked targets. This review offers an in-depth examination recent progress integration PROTAC technology oligonucleotides target traditionally proteins, emphasizing design principles mechanisms action innovative PROTACs.

Язык: Английский

Процитировано

0
Targeting neurodegenerative disease-associated protein aggregation with proximity-inducing modalities DOI

Ruixin Ge,

Miao Chen, Qingchao Li

и другие.

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Язык: Английский

Процитировано

0
Discovery of A First-in-class Protein Arginine Methyltransferase 1 (PRMT1) Degrader for Nonenzymatic Functions Studies DOI
Chao Ma, Hong‐Wei Sun, Chang Shen

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 291, С. 117625 - 117625

Опубликована: Апрель 14, 2025

Язык: Английский

Процитировано

0
DNA Nanotechnology for Application in Targeted Protein Degradation DOI
Yang Xiao, Xinyi Guo, Weiwei Zhang

и другие.

ACS Biomaterials Science & Engineering, Год журнала: 2024, Номер 10(11), С. 6814 - 6827

Опубликована: Окт. 5, 2024

DNA is a kind of flexible and versatile biomaterial for constructing nanostructures nanodevices. Due to high biocompatibility programmability easy modification fabrication, nanotechnology has emerged as powerful tool application in intracellular targeted protein degradation. In this review, we summarize the recent advances design mechanism degradation technologies such hydrolysis chimeras, lysosomal autophagy based Subsequently, introduce nanotechnologies cascade circuits, nanostructures, dynamic machines. Moreover, present latest developments Finally, vision challenges are discussed.

Язык: Английский

Процитировано

0