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Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.
Sweis, Ramzi F; Wang, Zhi; Algire, Mikkel; Arrowsmith, Cheryl H; Brown, Peter J; Chiang, Gary G; Guo, Jun; Jakob, Clarissa G; Kennedy, Steven; Li, Fengling; Maag, David; Shaw, Bailin; Soni, Nirupama B; Vedadi, Masoud; Pappano, William N.
Afiliación
  • Sweis RF; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Wang Z; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Algire M; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Arrowsmith CH; Structural Genomics Consortium, University of Toronto , Toronto, ON M5G 1L7, Canada ; Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto , Toronto, ON M5G 2M9, Canada.
  • Brown PJ; Structural Genomics Consortium, University of Toronto , Toronto, ON M5G 1L7, Canada.
  • Chiang GG; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Guo J; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Jakob CG; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Kennedy S; Structural Genomics Consortium, University of Toronto , Toronto, ON M5G 1L7, Canada.
  • Li F; Structural Genomics Consortium, University of Toronto , Toronto, ON M5G 1L7, Canada.
  • Maag D; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Shaw B; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Soni NB; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • Vedadi M; Structural Genomics Consortium, University of Toronto , Toronto, ON M5G 1L7, Canada ; Department of Pharmacology and Toxicology, University of Toronto , Toronto, ON M5S 1A8, Canada.
  • Pappano WN; Discovery Research, AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
ACS Med Chem Lett ; 6(6): 695-700, 2015 Jun 11.
Article en En | MEDLINE | ID: mdl-26101576
ABSTRACT
A lack of useful small molecule tools has precluded thorough interrogation of the biological function of SMYD2, a lysine methyltransferase with known tumor-suppressor substrates. Systematic exploration of the structure-activity relationships of a previously known benzoxazinone compound led to the synthesis of A-893, a potent and selective SMYD2 inhibitor (IC50 2.8 nM). A cocrystal structure reveals the origin of enhanced potency, and effective suppression of p53K370 methylation is observed in a lung carcinoma (A549) cell line.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Med Chem Lett Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Med Chem Lett Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos