Discovery of 2,4-diaminopyrimidine derivatives as potent inhibitors of FAK capable of activating the Hippo pathway for the treatment of esophageal squamous cell carcinoma

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117328 - 117328

Published: Feb. 2, 2025

Language: Английский

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Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 1095 - 1095

Published: Feb. 27, 2025

Cancer remains a significant global public health challenge, with hepatocellular carcinoma (HCC) ranking among the top five malignancies in terms of mortality. Faberidilactone A, sesquiterpenoid dimer isolated from Inula japonica, exhibits potent cytotoxicity against various human tumor cell lines and demonstrates remarkable antitumor potential. In vitro studies using HepG2 cells revealed that faberidilactone A induces apoptosis ferroptosis, causes cycle arrest, enhances production intracellular reactive oxygen species (ROS), disrupts mitochondrial function. Mechanistic investigations via Western blot analysis indicated impedes proliferation by modulating signal transducer activator transcription 3 (STAT3) signaling pathway inhibits metastasis affecting focal adhesion kinase (FAK) pathway. vivo experiments zebrafish model demonstrated effectively suppresses dissemination anti-angiogenic properties. When concentration reached 10 µM, inhibition rates proliferation, migration, intersegmental vessels (ISVs) length were 76.9%, 72.6%, 46.2%, respectively. These findings underscore therapeutic potential as promising agent for HCC treatment.

Language: Английский

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Exploring Thieno/Furo[2,3-b]pyridines as new scaffolds for potential FAK inhibition: Design, synthesis, biological evaluation and in silico studies

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108392 - 108392

Published: March 1, 2025

Language: Английский

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Discovery of Potent Focal Adhesion Kinase (FAK) Inhibitor A8 with Enhanced Antitumor Activity

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117593 - 117593

Published: April 1, 2025

Language: Английский

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