Understanding the mechanism of action of pyrrolo[3,2-b]quinoxaline-derivatives as kinase inhibitors

TitleUnderstanding the mechanism of action of pyrrolo[3,2-b]quinoxaline-derivatives as kinase inhibitors
Publication TypeJournal Article
Year of Publication2020
AuthorsUnzue A., Jessen-Trefzer C., Spiliotopoulos D., Gaudio E., Tarantelli C., Dong J., Zhao H., Pachmayr J., Zahler S., Bernasconi E., Sartori G., Cascione L., Bertoni F., Śledź P., Caflisch A., Nevado C.
JournalRSC Medicinal Chemistry
Pagination -
Date Published2020
Type of ArticleResearch Article
Abstract

The X-ray structure of the catalytic domain of the EphA3 tyrosine kinase in complex with a previously reported type II inhibitor was used to design two novel quinoxaline derivatives, inspired by kinase inhibitors that have reached clinical development. These two new compounds were characterized by an array of cell-based assays and gene expression profiling experiments. A global chemical proteomics approach was used to generate the drug-protein interaction profile, which suggested suitable therapeutic indications. Both inhibitors, studied in the context of angiogenesis and in vivo in a relevant lymphoma model, showed high efficacy in the control of tumor size.

URLhttp://dx.doi.org/10.1039/D0MD00049C
DOI10.1039/D0MD00049C
pubindex

0255

Short TitleRSC Med. Chem.
Alternate JournalRSC Med. Chem.