Identification of Pim Kinases as Novel Targets for PJ34 with Confounding Effects in PARP Biology

被引:56
作者
Antolin, Albert A. [1 ]
Jalencas, Xavier [1 ]
Yelamos, Jose [2 ]
Mestres, Jordi [1 ]
机构
[1] IMIM Hosp del Mar Res Inst, Chemogen Lab, Res Program Biomed Informat, Barcelona 08003, Catalonia, Spain
[2] IMIM Hosp del Mar Res Inst, Dept Immunol, Res Program Canc, Barcelona 08003, Catalonia, Spain
关键词
POLY(ADP-RIBOSE); INHIBITION; EXPRESSION;
D O I
10.1021/cb300317y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Small molecules are widely used in chemical biology without complete knowledge of their target profile, at risk of deriving conclusions that ignore potential confounding effects from unknown off-target interactions. The prediction and further experimental confirmation of novel affinities for PJ34 on Pim1 (IC50 = 3.7 mu M) and Pim2 (IC50 = 16 mu M) serine/threonine kinases, together with their involvement in many of the processes relevant to PARP biology, questions the appropriateness of using PJ34 as a chemical tool to probe the biological role of PARP1 and PARP2 at the high micromolar concentrations applied in most studies.
引用
收藏
页码:1962 / 1967
页数:6
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