Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 μM in TR-FRET-based assay and IC50 value of 5.45 μM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2013.04.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bioactive Products Targeting C-Met As Potential Antitumour Drugs.
Anticancer 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.
[A Case Report of EGFR-TKIs Resistant Secondary MET Gene Amplified Lung Squamous Cell Carcinoma and Literature Review].
Zhongguo Fei Ai Za Zhi
November 2024
Department of Oncology, The Central Hospital of Shaoyang, Shaoyang 422000, China.
With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment.
View Article and Find Full Text PDF[Savolitinib Induced Pathological Complete Response in Non-small Cell Lung Cancer with MET Amplification: A Case Report].
Zhongguo Fei Ai Za Zhi
November 2024
Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300000, China.
Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs).
View Article and Find Full Text PDFExploring the therapeutic potential of natural compounds against hepatocellular carcinoma (HCC): a computational approach.
EXCLI J
November 2024
Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam-si, 13120, Korea.
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer related deaths globally. Despite advancements in treatment, drug resistance and adverse side effects have spurred the search for novel therapeutic strategies. This study aimed to investigate how the can inhibit key targets involved in HCC progression.
View Article and Find Full Text PDFMET Exon 14 Skipping and Novel Actionable Variants: Diagnostic and Therapeutic Implications in Latin American Non-Small-Cell Lung Cancer Patients.
Int J Mol Sci
December 2024
Centro de Genética y Genómica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago 7550000, Chile.
Targeted therapy indications for actionable variants in non-small-cell lung cancer (NSCLC) have primarily been studied in Caucasian populations, with limited data on Latin American patients. This study utilized a 52-genes next-generation sequencing (NGS) panel to analyze 1560 tumor biopsies from NSCLC patients in Chile, Brazil, and Peru. The RNA sequencing reads and DNA coverage were correlated to improve the detection of the actionable exon 14 skipping variant (METex14).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!