Discovery of dually acting small-molecule inhibitors of cancer-resistance relevant receptor tyrosine kinases EGFR and IGF-1R12. Issue 11 (9th September 2016)

• Record Type: Journal Article
• Authors: Hempel, Cornelius; Najjar, Abdulkarim; Totzke, Frank; Schächtele, Christoph; Sippl, Wolfgang; Ritter, Christoph; Hilgeroth, Andreas
• Is Part Of: MedChemComm. Volume 7:Issue 11(2016:Nov.)
• Page Start: 2159
• Page End: 2166
• Publication Date: 2016-09-09
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00329j
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Small-molecule inhibitors of cancer-relevant receptor tyrosine kinases EGFR and IGF-1R have been discovered. Abstract : Novel benzo-anellated furo- and pyrrolo[2, 3- b ]pyridines with a 4-benzylamine substitution have been evaluated as inhibitors of the epidermal growth factor receptor (EGFR). Substituent effects on the determined protein kinase affinity have been discussed based on varied benzylamine residues at the differently substituted molecular scaffolds. Docking studies were carried out in order to explore the potential binding modes of the novel inhibitors. The observed activity data encouraged the measurement of the inhibition of the insulin-like growth factor receptor (IGF-1R), which is known to play an important role in the cancer-resistance development against EGFR inhibitors via receptor heterodimerizations with IGF-1R. We identified novel dual inhibitors of both kinases and report their first cancer cell growth inhibition data.