Discovery of thieno [3, 2-d] pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3

…, J Deng, F Coppo, L Aquilani, TL Graybill…

Index: Disch, Jeremy S.; Evindar, Ghotas; Chiu, Cynthia H.; Blum, Charles A.; Dai, Han; Jin, Lei; Schuman, Eli; Lind, Kenneth E.; Belyanskaya, Svetlana L.; Deng, Jianghe; Coppo, Frank; Aquilani, Leah; Graybill, Todd L.; Cuozzo, John W.; Lavu, Siva; Mao, Cheney; Vlasuk, George P.; Perni, Robert B. Journal of Medicinal Chemistry, 2013 , vol. 56, # 9 p. 3666 - 3679

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Citation Number: 89

Abstract

The sirtuins SIRT1, SIRT2, and SIRT3 are NAD+ dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan- inhibitors of SIRT1/2/3 with nanomolar potency (eg, 11c: IC50= 3.6, 2.7, and 4.0 nM for ...