Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma DOI Creative Commons
Arnab Mukherjee,

Preeti Harigovind Yadav,

K. S. Mukunthan

et al.

Molecular Biotechnology, Journal Year: 2023, Volume and Issue: 66(10), P. 2792 - 2803

Published: Sept. 28, 2023

Abstract Lung adenocarcinoma (LUAD) is one of the most prevalent and leading causes cancer deaths globally, with limited diagnostic clinically significant therapeutic targets. Identifying genes processes involved in developing progressing LUAD crucial for effective targeted therapeutics improving patient outcomes. Therefore, study aimed to explore RNA sequencing data from The Cancer Genome Atlas (TCGA) gene expression profile datasets involving GSE10072, GSE31210, GSE32863 Gene Expression Omnibus (GEO) databases. differential downstream analysis determined biomarkers using a network-based approach. These targets predominantly enriched dysregulation mitotic cell cycle regulation revealed co-overexpression Aurora-A Kinase (AURKA) Targeting Protein Xklp2 (TPX2) high survival risk patients. hydrophobic residues AURKA–TPX2 interaction were considered as target site block autophosphorylation AURKA during cycle. tyrosine kinase inhibitor (TKI) dacomitinib demonstrated strong binding potential hinder TPX2, shielding destabilization. This silico lays foundation repurposing options impede Protein–Protein Interactions (PPIs) progression aid future translational investigations.

Language: Английский

Current advances and development strategies of orally bioavailable PROTACs DOI
Shenxin Zeng,

Yingqiao Ye,

Heye Xia

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 261, P. 115793 - 115793

Published: Sept. 7, 2023

Language: Английский

Citations

35
Hydrophobic tag tethering degrader as a promising paradigm of protein degradation: Past, present and future perspectives DOI

Si Ha,

Jiacheng Zhu,

Hua Xiang

et al.

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 35(8), P. 109192 - 109192

Published: Oct. 13, 2023

Language: Английский

Citations

17
Orally Bioavailable Proteolysis-Targeting Chimeras: An Innovative Approach in the Golden Era of Discovering Small-Molecule Cancer Drugs DOI Creative Commons
Rohan Kalyan Rej, Srinivasa Rao Allu, Joyeeta Roy

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(4), P. 494 - 494

Published: April 12, 2024

Proteolysis-targeting chimeras (PROTACs) are an emerging therapeutic modality that show promise to open a target space not accessible conventional small molecules via degradation-based mechanism. PROTAC degraders, due their bifunctional nature, which is categorized as ‘beyond the Rule of Five’, have gained attention distinctive approach for oral administration in clinical settings. However, development PROTACs with adequate bioavailability remains significant hurdle, largely large size and less than ideal physical chemical properties. This review encapsulates latest advancements orally delivered entered evaluation well developments highlighted recent scholarly articles. The insights methodologies elaborated upon this could be instrumental supporting discovery refinement novel degraders aimed at treatment various human cancers.

Language: Английский

Citations

7
Identification of a Sonically Activated Degrader of Methionine Adenosyltransferase 2A by an in Silico Approach Assisted with the Hole–Electron Analysis DOI
Huan He, Ziwei Wang,

Xueke Peng

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(1), P. 543 - 554

Published: Jan. 2, 2024

Small molecules capable of modulating methionine adenosyltransferase 2A (MAT2A) are significant interest in precise cancer therapeutics. Herein, we raised the hole–electron Coulombic attraction as a reliable molecular descriptor for predicting reactive oxygen generation capacity MAT2A inhibitors, based on which discovered compound H3 sonically activated degrader MAT2A. Upon sonication, can generate species to specifically degrade cellular via rapid oxidative reactions. Combination and sonication induced 87% depletion human colon cells, thus elevating its antiproliferation effects by 8-folds. In vivo, had favorable pharmacokinetic profile (bioavailability = 77%) ADME properties. Owing degradation merits, at dosage 10 mg/kg 31% tumor regression xenograft models. The significantly boosted antitumor potency potentially alleviate toxicity high-dose inhibitors normal cells tissues, especially liver.

Language: Английский

Citations

3
Drosophila as a Promising In Vivo Research Model for the Application and Development of Targeted Protein Inactivation Technologies DOI
Н. В. Дорогова, С. А. Федорова

Archives of Insect Biochemistry and Physiology, Journal Year: 2025, Volume and Issue: 118(3)

Published: March 1, 2025

ABSTRACT Technologies for controlled protein targeting allow the selective manipulations of proteins resulting in their degradation and/or loss function. Over past two decades, these technologies have overcome limitations genetic methods and become powerful tools biological research search new therapeutic approaches to disease treatment. Various inactivation been successfully applied a model organism such as Drosophila melanogaster . In this article, we overview capabilities prospects vivo testing developing modern targeting, analyzing efficacy at level solving fundamental problems.

Language: Английский

Citations

0
Advancements in Proteolysis Targeting Chimeras for Targeted Therapeutic Strategies in Alzheimer’s Disease DOI Creative Commons

Qiuzhi Zhou,

Weixia Wang, Chunchu Deng

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Language: Английский

Citations

0
Exploiting E3 Ligases for Lung Cancer Therapy: The Promise of DCAF-PROTACs DOI
Md Sadique Hussain, Lina Eltaib, Amita Rana

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 156001 - 156001

Published: May 1, 2025

Language: Английский

Citations

0
How to target membrane proteins for degradation: Bringing GPCRs into the TPD fold DOI Creative Commons
Bogusława Korona, Laura S. Itzhaki

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107926 - 107926

Published: Oct. 1, 2024

Language: Английский

Citations

1
Unveiling Potential Targeted Therapeutic Opportunities for Co-Overexpressed Targeting Protein for Xklp2 and Aurora-A Kinase in Lung Adenocarcinoma DOI Creative Commons
Arnab Mukherjee,

Preeti Harigovind Yadav,

K. S. Mukunthan

et al.

Molecular Biotechnology, Journal Year: 2023, Volume and Issue: 66(10), P. 2792 - 2803

Published: Sept. 28, 2023

Abstract Lung adenocarcinoma (LUAD) is one of the most prevalent and leading causes cancer deaths globally, with limited diagnostic clinically significant therapeutic targets. Identifying genes processes involved in developing progressing LUAD crucial for effective targeted therapeutics improving patient outcomes. Therefore, study aimed to explore RNA sequencing data from The Cancer Genome Atlas (TCGA) gene expression profile datasets involving GSE10072, GSE31210, GSE32863 Gene Expression Omnibus (GEO) databases. differential downstream analysis determined biomarkers using a network-based approach. These targets predominantly enriched dysregulation mitotic cell cycle regulation revealed co-overexpression Aurora-A Kinase (AURKA) Targeting Protein Xklp2 (TPX2) high survival risk patients. hydrophobic residues AURKA–TPX2 interaction were considered as target site block autophosphorylation AURKA during cycle. tyrosine kinase inhibitor (TKI) dacomitinib demonstrated strong binding potential hinder TPX2, shielding destabilization. This silico lays foundation repurposing options impede Protein–Protein Interactions (PPIs) progression aid future translational investigations.

Language: Английский

Citations

1