Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma

Autor:	Tammy M. Havener, Christopher R. M. Asquith, Gary L. Johnson, William J. Zuercher, Tuomo Laitinen, Michael P. East, David C Morris, Kaleb M. Naegeli, David H. Drewry, Carrow I. Wells
Rok vydání:	2019
Předmět:	musculoskeletal diseases Antineoplastic Agents Protein Serine-Threonine Kinases 01 natural sciences 03 medical and health sciences Cell Line Tumor Drug Discovery Chordoma medicine Humans Epidermal growth factor receptor Protein Kinase Inhibitors Cell Proliferation 030304 developmental biology Cyclin EGFR inhibitors 0303 health sciences biology Chemistry Kinase HEK 293 cells Intracellular Signaling Peptides and Proteins medicine.disease In vitro 0104 chemical sciences ErbB Receptors Molecular Docking Simulation 010404 medicinal & biomolecular chemistry HEK293 Cells Cell culture Drug Design Aminoquinolines Quinazolines Cancer research biology.protein Molecular Medicine Protein Binding
Zdroj:	Journal of Medicinal Chemistry. 62:4772-4778
ISSN:	1520-4804 0022-2623
DOI:	10.1021/acs.jmedchem.9b00350
Popis:	We describe the design of a set of inhibitors to investigate the relationship between cyclin G associated kinase (GAK) and epidermal growth factor receptor (EGFR) in chordoma bone cancers. These compounds were characterized both in vitro and using in cell target engagement assays. The most potent chordoma inhibitors were further characterized in a kinome-wide screen demonstrating narrow spectrum profiles. While we observed a direct correlation between EGFR and antiproliferative effects on chordoma, GAK inhibition appeared to have only a limited effect.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::737bf7e7c8e9eb225acd64c9e2e58c05 https://doi.org/10.1021/acs.jmedchem.9b00350 Zobrazit plný text záznamu