Pyrimidino-thiazolyl carbonitriles were prepared that are potent VEGFR-2 (KDR) kinase inhibitors. The modification of lead structures resulted in 3m which exhibited the best overall profile in KDR inhibitory activity, iv/po pharmacokinetics, and reduced hERG affinity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2005.11.089 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of Electric Fields on the Mechanical Mechanism of Regorafenib-VEGFR2 Interaction to Enhance Inhibition of Hepatocellular Carcinoma.
Biomolecules
January 2025
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
The interaction between molecular targeted therapy drugs and target proteins is crucial with regard to the drugs' anti-tumor effects. Electric fields can change the structure of proteins, which determines the interaction between drugs and proteins. However, the regulation of the interaction between drugs and target proteins and the anti-tumor effects of electric fields have not been studied thoroughly.
View Article and Find Full Text PDFSelenium-Chondroitin Sulfate Nanoparticles Inhibit Angiogenesis by Regulating the VEGFR2-Mediated PI3K/Akt Pathway.
Mar Drugs
January 2025
College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (NaSeO) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown.
View Article and Find Full Text PDFStromal PDGFR-beta expression is a prognostic factor in high-grade serous ovarian cancer patients but is it also predictive for response to antiangiogenic treatment?
J Cancer Res Clin Oncol
January 2025
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Objective: In advanced ovarian cancer, the majority of patients receive anti-angiogenic treatment with bevacizumab. However, its use is often associated with severe side effects, and not all patients benefit from the therapy. Currently, there are no reliable biomarkers to predict response to treatment.
View Article and Find Full Text PDFEndothelial FOXM1 and Dab2 promote diabetic wound healing.
JCI Insight
January 2025
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor-dependent (VEGF-dependent) angiogenesis remain unclear. In our study, the molecular underpinnings of endothelial dysfunction in diabetes are investigated, focusing on the roles of disabled-2 (Dab2) and Forkhead box M1 (FOXM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high-glucose-treated primary mouse skin endothelial cells.
View Article and Find Full Text PDFDiscovery of novel tris-1,2,3-triazole-based hybrids as VEGFR2 inhibitors with potent anti-proliferative and cytotoxicity through apoptosis induction.
Bioorg Chem
February 2025
Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002 Saudi Arabia. Electronic address:
The discovery of novel anti-cancer drugs motivated us to synthesize a new series of triple 1,2,3-triazole-based arm scaffolds featuring distinct un functionalized alkyl and/or aryl side chains with possible anti-cancer action using the click chemistry approach under both conventional and green microwave irradiation (MWI) methods. The Cu(I) catalyzed cycloaddition reaction of targeted tris-alkyne with un functionalized aliphatic and aromatic azides has been adopted as an efficient approach for synthesizing the desired click adducts. Microwave irradiation improved the synthetic processes, resulting in higher yields and faster reaction times.
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!