HSP90 inhibitor NVP-HSP990 alleviates rotavirus infection DOI Creative Commons
Yi Cao,

Q Y Zhu,

Xiaoping Wu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 16, 2023

Abstract Rotavirus (RV) infection is a significant cause of hospitalization and mortality in infants young children. Although conventional symptomatic treatments usually appear effective, tens thousands children still die each year due to the absence safe effective anti-RV drugs. Heat shock protein 90 (HSP90) required for efficient viral infection; however, unsatisfactory antiviral efficacy toxicity, there has been no HSP90-targeting agents applied clinical therapy currently. Here, we demonstrated that NVP-HSP990, novel small-molecule HSP90 inhibitor with excellent oral bioavailability brain penetration, was potent RV much bigger selectivity index (SI) than traditional HSP990 inhibitors. NVP-HSP990 potently inhibited replication vitro without blocking establishment. remarkably restored gene expressions most KEGG pathways disturbed by intestinal cells, except some inflammatory (IL-17, TNF, etc.). To be noted, significantly altered MAPK signaling pathway RV-induced activation as well disruption tight junctions Caco-2 cells. More importantly, effectively alleviated diarrhea, competently replication, obviously prevented pathological lesions intestine BALB/c suckling mice. Therefore, our results suggested can promising drug candidate against infection.

Language: Английский

Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies DOI Creative Commons

Wei‐Fang Zuo,

Qiwen Pang, Xinyu Zhu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 4, 2024

Language: Английский

Citations

11
Heat Shock Proteins, a Double-Edged Sword: Significance in Cancer Progression, Chemotherapy Resistance and Novel Therapeutic Perspectives DOI Open Access
Dominika Kunachowicz, Magdalena Król-Kulikowska,

Wiktoria Raczycka

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1500 - 1500

Published: April 14, 2024

Heat shock proteins (Hsps) are involved in one of the adaptive mechanisms protecting cells against environmental and metabolic stress. Moreover, large role these carcinogenesis process, as well chemoresistance, was noticed. This review aims to draw attention possibilities using Hsps developing new cancer therapy methods, indicate directions for future research on this topic. In order discuss matter, a thorough latest scientific literature carried out, taking into account importance selected from Hsp family, including Hsp27, Hsp40, Hsp60, Hsp70, Hsp90 Hsp110. One more characteristic features all is that they play multifaceted progression, which makes them an obvious target modern anticancer therapy. Some researchers emphasize directly inhibiting action proteins. turn, others point their possible use design vaccines, would work by inducing immune response various types cancer. Due possibilities, it believed may contribute progress oncoimmunology, thus help development therapies, be characterized higher effectiveness lower toxicity patients.

Language: Английский

Citations

8
Recent developments of HSP90 inhibitors: an updated patent review (2020-present) DOI
Liu Jian-feng,

Huangliang Shu,

Qinxin Xia

et al.

Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: 34(1-2), P. 1 - 15

Published: Feb. 1, 2024

Introduction The 90-kDa heat shock protein (HSP90) functions as a molecular chaperone, it assumes significant role in diseases such cancer, inflammation, neurodegeneration, and infection. Therefore, the research development of HSP90 inhibitors have garnered considerable attention.

Language: Английский

Citations

6
Hsp90 Promotes Gastric Cancer Cell Metastasis and Stemness by Regulating the Regional Distribution of Glycolysis‐Related Metabolic Enzymes in the Cytoplasm DOI Creative Commons
Shiya Liu,

Gaigai Shen,

Xuanyu Zhou

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

Heat-shock protein 90 (Hsp90) plays a crucial role in tumorigenesis and tumor progression; however, its mechanism of action gastric cancer (GC) remains unclear. Here, the Hsp90 GC metabolism is focus this research. High expression tissues can interact with glycolysis, collectively affecting prognosis clinical samples. Both vitro vivo experiments demonstrate that able to regulate migration stemness properties cells. Metabolic phenotype analyses indicate influences glycolytic metabolism. Mechanistically, interacts glycolysis-related enzymes, forming multienzyme complexes enhance glycolysis efficiency yield. Additionally, binds cytoskeleton-related proteins, regulating regional distribution enzymes at cell margin lamellar pseudopods. This effect could lead local increase efficient energy supply from further promoting epithelial-mesenchymal transition (EMT) metastasis. In summary, Hsp90, through interaction metabolic related forms multi-enzyme regulates by dynamic cytoskeletal adjustments, thereby These conclusions also support potential for combined targeted approach involving cytoskeleton therapy.

Language: Английский

Citations

4
Comparison between conventional, grinding, and microwave synthesis of methylpyrazoles as VEGFR-2/HSP90 dual inhibitors DOI
Ebtehal M. Husseiny, Rana M. Abdelnaby, Najla Altwaijry

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: March 31, 2025

Aim Embracing structure extension and substitution variation, methylpyrazolones 2–6 dimethylpyrazoles 8–14 were synthesized as VEGFR-2/HSP90 dual inhibitors.

Language: Английский

Citations

0
ALK-based dual inhibitors: Focus on recent development for non-small cell lung cancer therapy DOI

Qiu-Ge Liu,

Ji Wu, Ziyue Wang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117646 - 117646

Published: April 17, 2025

Language: Английский

Citations

0
Progression and Expansion of ALK Inhibitors Against NSCLC: A Dual Target Approach DOI

Shreya Kumari,

Mymoona Akhter, Ghanshyam Das Gupta

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 293, P. 117722 - 117722

Published: May 5, 2025

Language: Английский

Citations

0
Molecular docking analysis of guaiacin and chalcone from nutmeg (Myristica fragrans) as novel HSP90A inhibitors for skin cancer treatment DOI

Muhammad Zhafran Arrafi,

A Cahyani,

Nada Nikita Sitohang

et al.

Pharmacy Reports, Journal Year: 2025, Volume and Issue: 3(3), P. 73 - 73

Published: May 4, 2025

Skin cancer represents one of the most prevalent malignancies globally, with Indonesia reporting third highest incidence among types. Despite advances in treatment, there remains a critical need for novel therapeutic agents. Heat Shock Protein 90 Alpha (HSP90A) has emerged as promising target therapy due to its role stabilizing oncogenic proteins. This study aimed evaluate potential guaiacin and chalcone from nutmeg (Myristica fragrans) HSP90A inhibitors skin treatment through computational analysis. Molecular docking was performed using AutoDock Tools crystal structure (PDB ID: 2VCJ). The compounds were assessed binding affinity, molecular interactions, drug-likeness properties according Lipinski's Rule Five. Redocking validation yielded an RMSD 1.24 Å, confirming protocol reliability. Guaiacin demonstrated affinity (-7.40 kcal/mol) key hydrogen bonds Asp93 Lys58, while showed moderate (-5.99 single bond Thr184. Both exhibited favorable drug-like high predicted gastrointestinal absorption. emerges natural inhibitor candidate energy exceeding stability threshold (-7.00 interactions residues ATP-binding pocket, providing foundation further development nutmeg-derived anticancer

Language: Английский

Citations

0
Discovery of acetophenone/piperazin-2-one hybrids as selective anti-TNBC cancer agents by causing DNA damage DOI
Jun Zhang, Yuting Liao, Wei Wang

et al.

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 108, P. 129802 - 129802

Published: May 20, 2024

Language: Английский

Citations

3
Rational Design of Peptide Inhibitors Targeting HSP90–CDC37 Protein–Protein Interaction DOI
Qiuyue Zhang, Ling Yan, Yuxuan Zhang

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(2), P. 125 - 138

Published: Jan. 1, 2024

Background: Specifically blocking HSP90–CDC37 interaction is emerging as a prospective strategy for cancer therapy. Aim: Applying kinase pseudopeptide rationale to the discovery of protein–protein (PPI) inhibitors. Methods: Pseudosubstrates were identified through sequence alignment and evaluated by biolayer interferometry assay, co-immunoprecipitation assay antiproliferation assay. Results: TAT-DDO-59120 was disrupt PPI directly binding HSP90, both extracellularly intracellularly. In addition, peptide showed ideal antiproliferative activity against colorectal cell HCT116 (IC50 = 12.82 μM). Conclusion: Compared with traditional method screening large compound library identify inhibitors, this rapid efficient strong purpose, which provides novel designing

Language: Английский

Citations

2