Int Immunopharmacol
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Published: April 2020
Acetaminophen (APAP)-induced hepatotoxicity comes among the most frequent humans' toxicities caused by drugs. So far, therapeutic interventions for such type of drug-induced toxicity are still limited. In the current study, we examined the influence of capmatinib (Cap), a novel c-Met inhibitor, on APAP-induced hepatotoxicity in mice when administered 2 h prior, 2 h post and 4 h post APAP-challenge. The results revealed that Cap administration significantly attenuated APAP-induced liver injury when administered only 2 h prior and post APAP-administration. Cap hepatoprotective effect was mediated by lowering the excessive formation of lipid peroxidation and nitrosative stress products caused by APAP. Besides, Cap attenuated APAP-induced overproduction and release of proinflammatory mediators like TNF-α, IL-1β, IL-17A, IL-6, and MCP-1. Cap treatment also led to avoidance of APAP-subsequent repair by abating APAP-induced elevation of hepatic IL-22 and PCNA expressions. In conclusion, c-Met receptor inhibition may be a potential strategy for alleviating APAP-hepatotoxicity, especially when administered in the early phase of intoxication.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.intimp.2020.106292 | DOI Listing |
Bioorg Chem
January 2025
Center for Preclinical Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:
In this study, we reported the discovery of a novel type II c-Met/Axl inhibitor, characterized by using 4-amino-7H-pyrrolo[2,3-d]pyrimidine as a hinge region binder. Through a systematic exploration of the structure-activity relationship, based on the clinically reported c-Met inhibitor BMS-777607, we identified the optimized compound 22a. 22a exhibited remarkable potency against c-Met and Axl kinases, with IC values of 1 nM and 10 nM, respectively, and demonstrated over 100-fold selectivity to other members of the TAM subfamily.
View Article and Find Full Text PDFBMC Pulm Med
January 2025
Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 127 Dong Ming Road, Zhengzhou, 450008, China.
Background: Mesenchymal to epithelial transition factor (MET) dysregulation in non-small-cell-lung-cancer (NSCLC) is understudied, with scant data on treatment outcomes.
Methods: We retrospectively examined 160 NSCLC patients: 125 with primary MET mutations (further classified into MET exon 14 (METex14) skipping mutations and primary MET amplifications) and 35 with secondary MET amplifications. Patients underwent varied treatments: Chemotherapy, Immune monotherapy, Crizotinib, or Savolitinib.
Cell Commun Signal
January 2025
Department of Oncology, The First Affiliated Hospital of Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi Province, 330006, China.
The hepatocyte growth factor (HGF) along with its receptor (c-MET) are crucial in preserving standard cellular physiological activities, and imbalances in the c-MET signaling pathway can lead to the development and advancement of tumors. It has been extensively demonstrated that immune checkpoint inhibitors (ICIs) can result in prolonged remission in certain patients. Nevertheless, numerous preclinical studies have shown that MET imbalance hinders the effectiveness of anti-PD-1/PD-L1 treatments through various mechanisms.
View Article and Find Full Text PDFJ Comp Eff Res
February 2025
Department of Epidemiology, Merck Healthcare KGaA, Darmstadt, Germany.
exon 14 ex14) skipping occurs in 3-4% of non-small-cell lung cancer (NSCLC) cases. Low frequency of this alteration necessitated open-label, single-arm trials to investigate MET inhibitors. Since broad MET biomarker testing was only recently introduced in many countries, there is a lack of historical real-world data from patients with ex14 skipping NSCLC receiving conventional therapies.
View Article and Find Full Text PDFAnticancer Agents Med Chem
January 2025
Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Unlabelled: Mesenchymal‒epithelial transition factor (c-Met), a receptortyrosine kinase (RTK), plays a vital role in cell proliferation, migration and invasion, and tumour metastasis.
Objective: With increasing duration of treatment, many tumours gradually develop drug resistance. Therefore, novel antitumour drugs need to be developed to treat patients with tumours.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.