RNA methylation: where to from here for hematological malignancies? DOI
Andrew A. Guirguis

Experimental Hematology, Journal Year: 2024, Volume and Issue: 143, P. 104694 - 104694

Published: Dec. 6, 2024

Language: Английский

Epigenetic Targets and Their Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis DOI

Xiaohui Miao,

Pan Liu, Yangyang Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117463 - 117463

Published: March 1, 2025

Language: Английский

Citations

2
Small molecule inhibitors targeting m6A regulators DOI Creative Commons

Guotai Feng,

Yongya Wu, Yuan Hu

et al.

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

Published: May 6, 2024

As the most common form of epigenetic regulation by RNA, N

Language: Английский

Citations

12
Lomitapide: Targeting METTL3 to Overcome Osimertinib Resistance in NSCLC Through Autophagy Activation DOI Creative Commons
Xiaohui Du, Congcong Zhang,

Ying Li

et al.

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 28, 2025

ABSTRACT Osimertinib resistance remains a significant challenge in the treatment of non‐small cell lung cancer (NSCLC). N 6 ‐methyladenosine (m A) modifications are closely linked to various mechanisms anticancer and autophagy, offering new avenues for targeted therapies. However, role m A‐mediated autophagy osimertinib‐resistant NSCLC is still unclear. In this study, we utilized multi‐omics sequencing analysis found that overexpression A methyltransferase METTL3 contributes osimertinib NSCLC. Importantly, identified positively regulates expression autophagy‐related gene ubiquinone‐cytochrome C reductase complex assembly factor 2 ( UQCC2 ) through an A‐dependent mechanism. Further, confirmed knockdown leads downregulation triggers activation. Interestingly, lomitapide, cholesterol‐lowering drug, was repurposed enhance sensitivity cells therapy by inhibiting METTL3, which turn activated autophagy‐associated death pathways, reversing resistance. This study emphasizes critical METTL3/UQCC2 axis autophagy‐mediated drug positions lomitapide as promising inhibitor inducer with potential therapeutic effects, either alone or combination other agents, patients

Language: Английский

Citations

1
Post‐Translational Modifications of RNA‐Modifying Proteins in Cellular Dynamics and Disease Progression DOI Creative Commons
Yunfan Lin, Pei Lin, Ye Lu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(44)

Published: Oct. 8, 2024

Abstract RNA‐modifying proteins, classified as “writers,” “erasers,” and “readers,” dynamically modulate RNA by adding, removing, or interpreting chemical groups, thereby influencing stability, functionality, interactions. To date, over 170 distinct modifications more than 100 enzymes have been identified, with ongoing research expanding these numbers. Although significant progress has made in understanding modification, the regulatory mechanisms that govern proteins themselves remain insufficiently explored. Post‐translational (PTMs) such phosphorylation, ubiquitination, acetylation are crucial modulating function behavior of proteins. However, full extent PTM influence on their role disease development remains to be fully elucidated. This review addresses gaps offering a comprehensive analysis roles PTMs play regulating Mechanistic insights provided into how alter biological processes, contribute cellular function, drive progression. In addition, current landscape is examined, highlighting therapeutic potential targeting for precision medicine. By advancing networks, this seeks facilitate effective strategies inspire future critical area

Language: Английский

Citations

4
Patent landscape of small molecule inhibitors of METTL3 (2020-present) DOI
Zhixing Wu, Alexis R. Smith, Zhijian Qian

et al.

Expert Opinion on Therapeutic Patents, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: Dec. 25, 2024

Introduction Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' for RNA m6A methylation, accounting almost all mRNA modifications. Recent studies reveal that METTL3 implicated development and progression of various types cancers. Targeting small molecule inhibitors represents a promising therapeutic strategy cancer.

Language: Английский

Citations

4
METTL14‐mediated m6A modification of ZFP14 inhibits clear cell renal cell carcinoma progression via promoting STAT3 ubiquitination DOI Creative Commons

Zhuonan Liu,

Tianshui Sun,

Zhe Zhang

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Abstract Therapeutic options for advanced clear cell renal carcinoma (ccRCC) are currently inadequate. Earlier research has shown that the enzyme methyltransferase‐like 14 (METTL14) can suppress ccRCC development through modification of N6‐methyladenosine (m6A). This study further explored its complex biological functions and underlying molecular mechanisms. Here, we identified zinc finger protein (ZFP14) as a novel target METTL14‐mediated m6A, under‐expression was associated with tumourigenesis progression. Detailed investigations revealed METTL14 interacted directly 3′ untranslated region ZFP14 mRNA, promoting m6A at two specific sites. These modifications were recognised by insulin‐like growth factor 2 mRNA‐binding (IGF2BP2), which stabilised enhanced expression mRNA. Functionally, METTL14/ZFP14 axis suppressed in vitro growth, migration invasiveness vivo proliferation metastasis cells. potentially regulated numbers transcripts, among matrix metalloproteinase 1/3 (MMP1/3) validated to be under‐expressed ZFP14. Crucially, signal transducer activator transcription 3 (STAT3), augmenting K48‐linked ubiquitination destabilising it via proteasome pathway. Moreover, repressed well decreasing MMP1/3 levels under‐expressing STAT3. observations confirmed served both significant tumour suppressor ccRCC, shedding light on cellular operations opening up possibilities therapeutic strategies. Key points is enhances mRNA stability IGF2BP2 reader ccRCC. promotes degradation STAT3 enhancing ubiquitination, inhibiting

Language: Английский

Citations

0
Development of 3-Arylaminothiophenic-2-carboxylic Acid Derivatives as New FTO Inhibitors Showing Potent Antileukemia Activities DOI

Deyan Zhang,

Lu Liu, Ming Li

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117444 - 117444

Published: Feb. 25, 2025

Language: Английский

Citations

0
Recent Advances in Medicinal Chemistry Strategies for the Development of METTL3 Inhibitors DOI

G. Li,

Wei Chen, Dan Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117560 - 117560

Published: March 1, 2025

Language: Английский

Citations

0
Targeted Degradation of METTL3 Against Acute Myeloid Leukemia and Gastric Cancer. DOI

Kyubin Hwang,

Ju‐Hyeon Bae,

Yoo-Lim Jhe

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 279, P. 116843 - 116843

Published: Sept. 6, 2024

Language: Английский

Citations

3
PROTAC delivery in tumor immunotherapy: Where are we and where are we going? DOI
Yiyang Li, Yike Wu, Shugeng Gao

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 378, P. 116 - 144

Published: Dec. 11, 2024

Language: Английский

Citations

2