1054315-77-3Relevant articles and documents
4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors
Xu, Guozhang,Abad, Marta C.,Connolly, Peter J.,Neeper, Michael P.,Struble, Geoffrey T.,Springer, Barry A.,Emanuel, Stuart L.,Pandey, Niranjan,Gruninger, Robert H.,Adams, Mary,Moreno-Mazza, Sandra,Fuentes-Pesquera, Angel R.,Middleton, Steven A.
scheme or table, p. 4615 - 4619 (2009/04/08)
Members of a novel class of 4-amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones were identified as potent dual ErbB-2/EGFR kinase inhibitors using concept-guided design approach. These compounds inhibited the growth of ErbB-2 over-expressing human tumor cell lines (BT474, N87, and SK-BR-3) in vitro. Compound 15 emerged as a key lead and showed significant ability to inhibit growth factor-induced receptor phosphorylation in SK-BR-3 cells (IC50 = 54 nM) and cellular proliferation in vitro (IC50 = 14, 58, and 58 nM for BT474, N87, and SK-BR-3 respectively). The X-ray co-crystal structure of EGFR with a close analog (17) was determined and validated our design rationale.
