Discovery of a Potent Importin Inhibitor for Cancer Treatment DOI
Dirk Trauner, Xiang Ji

Synfacts, Journal Year: 2022, Volume and Issue: 18(12), P. 1369 - 1369

Published: Nov. 17, 2022

Key words importin inhibitors - castration-resistant prostate cancer (CRPC) daphnane diterpenoids (DDs)

Language: Английский

Nuclear transport proteins: structure, function, and disease relevance DOI Creative Commons
Yang Yang,

Lu Guo,

Lin Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 10, 2023

Abstract Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport a fundamental cellular process that regulates many macromolecules within nuclear or cytoplasmic compartments. In humans, approximately 60 are involved in transport, nucleoporins form membrane-embedded pore complexes, karyopherins cargoes through these Ran system ensure directed rapid transport. Many play additional essential roles mitosis, biomolecular condensation, gene transcription. Dysregulation linked to major human diseases such as cancer, neurodegenerative diseases, viral infections. Selinexor (KPT-330), an inhibitor targeting export factor XPO1 (also known CRM1), was approved 2019 treat two types blood cancers, dozens clinical trials ongoing. This review summarizes three decades research data this field but focuses on structure function individual from recent studies, providing cutting-edge holistic view role health disease. In-depth knowledge rapidly evolving has potential bring new insights into biology, pathogenic mechanisms, therapeutic approaches.

Language: Английский

Citations

62
Tigliane and daphnane diterpenoids from Thymelaeaceae family: chemistry, biological activity, and potential in drug discovery DOI Creative Commons
Kouharu Otsuki, Wei Li

Journal of Natural Medicines, Journal Year: 2023, Volume and Issue: 77(4), P. 625 - 643

Published: June 9, 2023

Abstract Tigliane and daphnane diterpenoids are characteristically distributed in plants of the Thymelaeaceae family as well Euphorbiaceae structurally diverse due to presence polyoxygenated functionalities polycyclic skeleton. These known toxic components, while they have been shown exhibit a wide variety biological activities, such anti-cancer, anti-HIV, analgesic activity, attracting attention field natural product drug discovery. This review focuses on naturally occurring tigliane from provides an overview their chemical structure, distribution, isolation, structure determination, synthesis, with prime focus recent findings.

Language: Английский

Citations

22
DHODH inhibition represents a therapeutic strategy and improves abiraterone treatment in castration-resistant prostate cancer DOI

Shaoqiang Guo,

Miaomiao Miao,

Yufeng Wu

et al.

Oncogene, Journal Year: 2024, Volume and Issue: 43(19), P. 1399 - 1410

Published: March 13, 2024

Language: Английский

Citations

7
Highly anticipated natural diterpenoids as an important source of new drugs in 2013–2023 DOI
Yingjie Wang, Peng Tang,

Wen‐Chao Tu

et al.

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: 36(1), P. 109955 - 109955

Published: May 1, 2024

Language: Английский

Citations

7
Nuclear Import and Export of YAP and TAZ DOI Open Access

Michael Kofler,

András Kapùs

Cancers, Journal Year: 2023, Volume and Issue: 15(20), P. 4956 - 4956

Published: Oct. 12, 2023

Yes-associated Protein (YAP) and its paralog Transcriptional Coactivator with PDZ-binding Motif (TAZ) are major regulators of gene transcription/expression, primarily controlled by the Hippo pathway cytoskeleton. Integrating an array chemical mechanical signals, they impact growth, differentiation, regeneration. Accordingly, also play key roles in tumorigenesis metastasis formation. Their activity is regulated their localization, that is, pathway- and/or cytoskeleton-controlled cytosolic or nuclear sequestration. While many details such prevailing retention models have been elucidated, much less known about actual traffic: import export. Although size not far from cutoff for passive diffusion through pore complex (NPC), do contain any classic localization (NLS) export signal (NES), evidence has accumulating shuttling involves mediated thus regulatable/targetable processes. The aim this review to summarize emerging information/concepts nucleocytoplasmic shuttling, encompassing relevant structural requirements (NLS, NES), transport receptors (NTRs, karyophererins), NPC components, along potential mechanisms regulation. dissecting vs. often challenging, picture suggests YAP/TAZ shuttles across via multiple, non-exclusive, mechanisms, constituting a novel intriguing facet biology.

Language: Английский

Citations

14
A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2 DOI
Lu Gan, Qiwei Jiang,

Dong Huang

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Language: Английский

Citations

6
Terpenes and Terpenoids Conjugated with BODIPYs: An Overview of Biological and Chemical Properties DOI Creative Commons
Jarmila Stanková, Michal Jurášek, Marián Hajdúch

et al.

Journal of Natural Products, Journal Year: 2024, Volume and Issue: 87(4), P. 1306 - 1319

Published: March 14, 2024

Advancements in small-molecule research have created the need for sensitive techniques to accurately study biological processes living systems. Fluorescent-labeled probes become indispensable tools, particularly those that use boron–dipyrromethene (BODIPY) dyes. Terpenes and terpenoids are organic compounds found nature offer diverse activities, BODIPY-based play a crucial role studying these compounds. Monoterpene–BODIPY conjugates exhibited potential staining bacterial fungal cells. Sesquiterpene–BODIPY derivatives been used sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), indicating their drug development. Owing unique properties, diterpenes investigated using BODIPY evaluate mechanisms of action. Triterpene–BODIPY synthesized studies, with different spacers affecting cytotoxicity. Fluorescent probes, inspired by terpenoid-containing vitamins, also developed. Derivatives tocopherol, coenzyme Q10, vitamin K1 can provide insights into oxidation–reduction abilities. All applications, including cell membranes investigate immune responses antioxidant properties. Further this field help better understand terpenes various contexts.

Language: Английский

Citations

5
A green and simple method for enrichment of major diterpenoids from the buds of Wikstroemia chamaedaphne with macroporous resins and their activation of latent human immunodeficiency virus activity DOI Creative Commons
Shi-Fei Li,

Gong-Lu Li,

D Chen

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 272, P. 132932 - 132932

Published: June 1, 2024

In this study, a green and efficient enrichment method for the four majors active diterpenoid components: pimelotide C, A, simplexin, 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate in buds of Wikstroemia chamaedaphne was established using macroporous resin chromatography. The adsorption desorption rates seven resins were compared static tests. D101 exhibited best performance. Static dynamic tests performed to determine purification important bioactive diterpenoids W. chamaedaphne. Diterpenoid extracts obtained by from crude Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated that most enriched extracts. These results confirmed could be technology, showed more activation latent human immunodeficiency virus. This study provides novel strategy discovering low-toxicity latency-reversing agents potential basis comprehensive development clinical application

Language: Английский

Citations

5
Meroterpenoids from Daphne genkwa shows promising in vitro antitumor activity via inhibiting PI3K/Akt/mTOR signaling pathway in A549 cells DOI

Ren‐Fen Ma,

Hu Liu,

Xuechun Zhao

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 140, P. 106803 - 106803

Published: Aug. 23, 2023

Language: Английский

Citations

10
Insights of Affinity-Based Probes for Target Identification in Drug Discovery DOI
Hui Wang, Li Liu,

Zhoudong Zhang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 293, P. 117711 - 117711

Published: May 6, 2025

Language: Английский

Citations

0