Discovery of 3-(2-aminobenzo[d]thiazol-5-yl) benzamide derivatives as potent anticancer agents via ROR1 inhibition DOI

Fang Luo,

Jie Liu,

Rongtao Wang

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 117, P. 118011 - 118011

Published: Nov. 20, 2024

Language: Английский

Discovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models DOI
Guillaume Dutheuil,

Killian Oukoloff,

Julien Korac

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

METTL3 is the RNA methyltransferase predominantly responsible for addition of N6-methyladenosine (m6A), most abundant modification to mRNA. The prevalence m6A and activity expression have been linked appearance progression acute myeloid leukemia (AML), thereby making an attractive target cancer therapeutics. We report herein discovery optimization small-molecule inhibitors METTL3, culminating in selection EP652 as vivo proof-of-concept compound. potently inhibits enzymatic has favorable PK parameters, demonstrates efficacy preclinical oncology models, indicating that pharmacological inhibition a viable strategy treatment liquid solid tumors.

Language: Английский

Citations

2
Mechanistic insights into vascular biology via methyltransferase-like 3-driven N6-adenosine methylation of RNA DOI Creative Commons
Deshuang Zhang,

Zhixian Gou,

Yi Qu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 6, 2025

Recent advancements in the mechanistic comprehension of vascular biology have concentrated on METTL3-mediated N6-methyladenosine modification RNA, which modulates a spectrum RNA functionalities with precision. Despite extensive investigations into roles and mechanisms METTL3 within biology, holistic review elucidating their interconnections remains absent. This analysis endeavors to meticulously scrutinize involvement both physiological pathological paradigms biology. The findings this indicate that is indispensable for development functionality, predominantly through its regulatory influence pericytes, endothelial cells, smooth muscle hematopoietic stem cells. Conversely, aberrant activity implicated as risk factor, diagnostic biomarker, therapeutic target pathologies. comprehensive offers an exhaustive synthesis METTL3's role addressing existing knowledge gaps serving essential reference future research potential clinical applications.

Language: Английский

Citations

1
Methyltransferase-like 3-mediated RNA N6-methyladenosine contributes to immune dysregulation: diagnostic biomarker and therapeutic target DOI Creative Commons
Deshuang Zhang, Ting Xu, Xiaoxue Gao

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 24, 2025

Methyltransferase-like 3 (METTL3) plays a crucial role in post-transcriptional gene regulation. Substantial evidence links METTL3 to various immune dysfunctions, such as the suppression of antiviral immunity during viral infections and disruption tolerance conditions like autoimmune diseases, myeloid leukemia, skin cancers, anticancer immunotherapy. However, thorough review analysis this is currently missing, which limits understanding METTL3’s mechanisms significance dysfunctions. This aims elucidate roles these issues, highlighting its connections proposing new insights into modulation responses. Analysis results suggest that hampers immunity, worsens replication infection, disrupts tolerance; conversely, regulating enhances facilitates clearance. Moreover, clinical data corroborates findings, showing overexpression associated with increased susceptibility conditions. establishes theoretical basis for considering novel regulator, an important diagnostic biomarker, potential target treating

Language: Английский

Citations

0
Understanding how methyltransferase-like 3 functions in lung diseases: From pathogenesis to clinical application DOI Open Access
Deshuang Zhang,

Zhixian Gou,

Yi Qu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117421 - 117421

Published: Sept. 6, 2024

Language: Английский

Citations

3
The indispensability of methyltransferase-like 3 in the immune system: from maintaining homeostasis to driving function DOI Creative Commons

Mingfu Zhang,

Zhixian Gou,

Yi Qu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 2, 2024

Methyltransferase-like 3(METTL3), recognized as the primary N

Language: Английский

Citations

3
Ancient wisdom and modern innovations: Methods of administering healing DOI Creative Commons
Aila Akosua Kattner

Biomedical Journal, Journal Year: 2024, Volume and Issue: 47(4), P. 100773 - 100773

Published: July 24, 2024

This issue of the Biomedical Journal highlights major advancements in drug delivery, including aptamer-functionalized liposomes and nanozymes. A new biomarker combination shows promise for improved diagnosis idiopathic pulmonary fibrosis. Mesenchymal stem cells are suggested to mitigate inflammation systemic lupus erythematosus, a potential positive feedback loop driven by prevalent mRNA modification is enhance NSCLC progression. Additional articles explore pathological impact on autophagy leading muscle dysfunction, benefits integrating an orphan with standard therapy glioblastoma patients, influence transcriptional super-enhancers early-stage esophageal squamous cell carcinoma. Finally, this provides insights into roles different Blastocystis subtypes, use laser light treating infantile hemangioma.

Language: Английский

Citations

0
Discovery of 3-(2-aminobenzo[d]thiazol-5-yl) benzamide derivatives as potent anticancer agents via ROR1 inhibition DOI

Fang Luo,

Jie Liu,

Rongtao Wang

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 117, P. 118011 - 118011

Published: Nov. 20, 2024

Language: Английский

Citations

0