Discovery and biological evaluation of a novel and highly potent JAK2 inhibitor for the treatment of triple negative breast cancer DOI Creative Commons
Ying Miao, Shudan Yang, Fang Zhang

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 29, 2025

Janus kinase 2 (JAK2) is considered an attractive target for the treatment of triple-negative breast cancer (TNBC). Herein, we discovered six JAK2 inhibitors using structure-based virtual screening and molecular docking. Among them, JNN-5 was best compound. It indicated strong inhibitory effects on in nanomolar range (IC50 = 0.41 ± 0.03 nM), high selectivity over JAK1 JAK3 (selectivity index (SI) > 73.17). Moreover, dynamics (MD) simulation exhibited that bound with stability to JH1. Cellular assays revealed displayed antiproliferative activities TNBC cell lines (MDA-MB-468, MDA-MB-213, HCC70, MDA-MB-157). significantly reduced migration HUVECs dose-dependence. had a significant effect multidrug-resistant MDA-MB-231/ADR 0.37 0.02 μM). These data demonstrate may be highly effective selective antitumor compound TNBC.

Language: Английский

Halofuginone Disrupted Collagen Deposition via mTOR‐eIF2α‐ATF4 Axis to Enhance Chemosensitivity in Ovarian Cancer DOI Creative Commons
Wenxin Li, Yenan Wu, Yanan Zhang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

The interplay between cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) mediates progress, metastasis, therapy resistance. However, strategy of targeting ECM remodeling to enhance chemosensitivity in ovarian cancer remains elusive. Here, a 22-gene matrisome signature predicts chemotherapy response survival cancer. dense, collagen-rich secreted by CAFs harbors more M2 tumor-associated macrophages (TAMs) than the looser based on single cell RNA-seq (scRNA-seq) cancer, suggesting promising approach collagen remodel ECM. An integrated analysis identifies type I alpha 1 chain (COL1A1) as major component that contributes chemoresistance poor prognosis, highlighting its potential therapeutic target. Halofuginone (HF), clinically active derivative febrifugine, is identified COL1A1-targeting natural compound screening Encyclopedia Traditional Chinese Medicine (ETCM). Mechanistically, HF inhibits COL1A1 production via mTOR-eIF2α-ATF4 axis CAFs. Notably, disrupts deposition promotes CD8+ T infiltration, partially M2-M1 macrophage polarization chemosensitivity. Overall, findings suggest combined with effective treatment for

Language: Английский

Citations

1
Silibinin, a PLC-β3 inhibitor, inhibits mast cell activation and alleviates OVA-induced asthma DOI

Tzu‐Ting Chen,

Juan-Cheng Yang,

Guan-Yu Chen

et al.

Molecular Immunology, Journal Year: 2025, Volume and Issue: 178, P. 76 - 86

Published: Jan. 26, 2025

Language: Английский

Citations

0
Discovery and biological evaluation of a novel and highly potent JAK2 inhibitor for the treatment of triple negative breast cancer DOI Creative Commons
Ying Miao, Shudan Yang, Fang Zhang

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 29, 2025

Janus kinase 2 (JAK2) is considered an attractive target for the treatment of triple-negative breast cancer (TNBC). Herein, we discovered six JAK2 inhibitors using structure-based virtual screening and molecular docking. Among them, JNN-5 was best compound. It indicated strong inhibitory effects on in nanomolar range (IC50 = 0.41 ± 0.03 nM), high selectivity over JAK1 JAK3 (selectivity index (SI) > 73.17). Moreover, dynamics (MD) simulation exhibited that bound with stability to JH1. Cellular assays revealed displayed antiproliferative activities TNBC cell lines (MDA-MB-468, MDA-MB-213, HCC70, MDA-MB-157). significantly reduced migration HUVECs dose-dependence. had a significant effect multidrug-resistant MDA-MB-231/ADR 0.37 0.02 μM). These data demonstrate may be highly effective selective antitumor compound TNBC.

Language: Английский

Citations

0