7-(4H-1,2,4-Triazol-3-yl)benzo[c][2,6]naphthyridines: a novel class of Pim kinase inhibitors with potent cell antiproliferative activity.
Bioorg Med Chem Lett
; 21(22): 6687-92, 2011 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-21982499
ABSTRACT
A novel class of pan-Pim kinase inhibitors was designed by modifying the CK2 inhibitor CX-4945. Introduction of a triazole or secondary amide functionality on the C-7 position and 2'-halogenoanilines on C-5 resulted in potent inhibitors of the Pim-1 and Pim-2 isoforms, with many analogs active at single digit nanomolar concentrations. The molecules inhibited the phosphorylation at Serine 112 of the apoptosis effector BAD, and had potent antiproliferative effects on the AML cell line MV-4-11 (IC(50) <30 nM). This work delivers an excellent lead-optimization platform for Pim targeting anticancer therapies.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
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Proteínas Proto-Oncogênicas c-pim-1
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Naftiridinas
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Antineoplásicos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article