Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.
ACS Med Chem Lett
; 6(6): 695-700, 2015 Jun 11.
Article
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| 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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01-internacional
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MEDLINE
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En
Revista:
ACS Med Chem Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos