Structure-based tailoring of compound libraries for high-throughput screening: Discovery of novel EphB4 kinase inhibitors Supplementary Material
نویسندگان
چکیده
منابع مشابه
Structure-based tailoring of compound libraries for high-throughput screening: discovery of novel EphB4 kinase inhibitors.
High-throughput docking is a computational tool frequently used to discover small-molecule inhibitors of enzymes or receptors of known three-dimensional structure. Because of the large number of molecules in chemical libraries, automatic procedures to prune multimillion compound collections are useful for high-throughput docking and necessary for in vitro screening. Here, we propose an anchor-b...
متن کاملDevelopment and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors.
The kinase MEKK2 (MAP3K2) has recently been implicated in tumor growth and metastasis. Thus, selective inhibition of MEKK2 may be a novel strategy for cancer therapy. To identify inhibitors of MEKK2 kinase activity, we have developed a novel activity assay for MEKK2 based on the discovery that recombinant purified MEKK2 has intrinsic ATPase activity. This MEKK2 ATPase assay was validated for en...
متن کاملDesign and characterization of a functional library for NMR screening against novel protein targets.
In the past few years, NMR has been extensively utilized as a screening tool for drug discovery using various types of compound libraries. The designs of NMR specific chemical libraries that utilize a fragment-based approach based on drug-like characteristics have been previously reported. In this article, a new type of compound library will be described that focuses on aiding in the functional...
متن کاملIdentification of Novel IGF1R Kinase Inhibitors by Molecular Modeling and High-Throughput Screening
The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to develop drug candidates that are superior to the existing experimental anti-IGF1R therapeuticals. To this end, targeted compound libraries were produced by virtual screening using molecular modeling and...
متن کاملStructure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4).
The tyrosine kinase EphB4 is an attractive target for drug design because of its recognized role in cancer-related angiogenesis. Recently, a series of commercially available xanthine derivatives were identified as micromolar inhibitors of EphB4 by high-throughput fragment-based docking into the ATP-binding site of the kinase domain. Here, we have exploited the binding mode obtained by automatic...
متن کامل