Discovery of A First-in-class Protein Arginine Methyltransferase 1 (PRMT1) Degrader for Nonenzymatic Functions Studies DOI
Chao Ma, Hong‐Wei Sun, Chang Shen

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117625 - 117625

Published: April 14, 2025

Language: Английский

Epigenetics in autosomal dominant polycystic kidney disease DOI
Zhipeng Yan, Feng Cao, Tingting Shao

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167652 - 167652

Published: Jan. 1, 2025

Language: Английский

Citations

0
Discovery of novel PRMT1 inhibitors: a combined approach using AI classification model and traditional virtual screening DOI Creative Commons

Jungan Zhang,

Yixin Ren,

Yun Teng

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 20, 2025

Protein arginine methyltransferases (PRMTs) play crucial roles in gene regulation, signal transduction, mRNA splicing, DNA repair, cell differentiation, and embryonic development. Due to its significant impact, PRMTs is a target for the prevention treatment of various diseases. Among PRMT family, PRMT1 most abundant ubiquitously expressed human body. Although extensive research has been conducted on PRMT1, reported inhibitors have not successfully passed clinical trials. In this study, deep learning was employed analyze characteristics existing construct classification model inhibitors. Through molecular docking, series potential were identified. The representative compound (compound 156) demonstrates stable binding protein by hybridization, dynamics simulations, free energy analyses. study discovered novel scaffolds

Language: Английский

Citations

0
PRMT1-Catalyzed NUSAP1 Methylation Enhances Notch2 Signaling and 5-FU Resistance in Gastric Cancer DOI Creative Commons

Feng Wang,

Steve Jiang,

Guoli Li

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract 5-Fluorouracil (5-FU) resistance remains a significant challenge in the treatment of gastric cancer, limiting its clinical efficacy. Our study identifies NUSAP1, nucleolar and spindle-associated protein, as key driver 5-FU cancer. Proteomic analyses 5-FU-resistant cancer cell lines revealed that NUSAP1 is significantly upregulated, functional studies demonstrated essential role promoting resistance, proliferation, migration, invasion, tumor growth. Mechanistic investigations undergoes asymmetric dimethylation (ADMA) at R418 R422, mediated by PRMT1, with R422 site being critical for function. interacts PEST domain Notch2 through site, inhibiting ubiquitination stabilizing expression, thereby activating signaling pathway. This pathway closely linked to progression chemoresistance. Inhibition PRMT1 or mutation abrogated NUSAP1’s ability stabilize regulate downstream signaling. These findings unveil novel mechanism which promotes highlight therapeutic potential targeting NUSAP1-Notch2 axis overcoming

Language: Английский

Citations

0
Apelin-13/APJ promotes neural stem cells to repair ischemic stroke DOI Creative Commons
Shuangmei Li,

Shihan Yuan,

Shujun Yang

et al.

Tissue and Cell, Journal Year: 2025, Volume and Issue: 95, P. 102872 - 102872

Published: March 22, 2025

Neural stem cell therapy is considered as a promising new for ischemic stroke. However, the therapeutic efficacy of neural cells (NSCs) hampered by effects cerebral ischemia and hypoxia, resulting in suboptimal performance. Drug stimulation can further improve NSCs stroke, among which small molecule peptide Apelin-13 could have potential. In this study, we simulated anoxic microenvironment oxygen-glucose deprivation (OGD) to observe improvement on treatment-related functions. Six hours OGD treatment suppressed viability NSCs, while 100 nM mitigated suppression. Additionally, reduced migration capability but enhanced ability under conditions. also increased rate apoptotic decreased ratio Bcl-2 Bax. environment, BDNF expression was elevated, level. APJ endogenous receptor Apelin-13. We knocked down observed that effect abolished environment compared with negative control group knockdown, upregulation brain derived neurotrophic factor (BDNF) lost. Our study found enhances fosters migration, diminishes apoptosis, augments conditions through receptor. The Apelin-13/APJ system may play beneficial role activating purpose treating This positive be mediated downstream effector protein, BDNF.

Language: Английский

Citations

0
Discovery of A First-in-class Protein Arginine Methyltransferase 1 (PRMT1) Degrader for Nonenzymatic Functions Studies DOI
Chao Ma, Hong‐Wei Sun, Chang Shen

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117625 - 117625

Published: April 14, 2025

Language: Английский

Citations

0