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

Unzue, Andrea; Jessen-Trefzer, Claudia; Spiliotopoulos, Dimitrios; Gaudio, Eugenio; Tarantelli, Chiara; Dong, Jing; Zhao, Hongtao; Pachmayr, Johanna; Zahler, Stefan; Bernasconi, Elena; Sartori, Giulio; Cascione, Luciano; Bertoni, Francesco; Sledz, Pawel; Caflisch, Amedeo und Nevado, Cristina (2020): Understanding the mechanism of action of pyrrolo[3,2-b]quinoxaline-derivatives as kinase inhibitors. In: Rsc Medicinal Chemistry, Vol. 11, No. 6: pp. 665-675

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 andin vivoin a relevant lymphoma model, showed high efficacy in the control of tumor size.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Pharmacy
• Subjects: 500 Science > 540 Chemistry
• Language: English