Identification of Pim Kinases as Novel Targets for PJ34 with Confounding Effects in PARP Biology
Identification of Pim Kinases as Novel Targets for PJ34 with Confounding Effects in PARP Biology
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DOI：
10.1021/cb300317y
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Mestres, Jordi
中科院分区：
文献类型：
--
作者：
Antolin, Albert A.;Jalencas, Xavier;Mestres, Jordi
小分子被广泛用于化学生物学，而不完全了解其目标特征，存在得出忽略未知脱靶相互作用的潜在混淆效应的结论的风险。PJ 34在Pim 1上的新亲和力的预测和进一步的实验证实（IC 50 = 3.7 μ M）和Pim 2（IC 50 = 16 μ M）丝氨酸/苏氨酸激酶，以及它们参与与PARP生物学相关的许多过程，质疑使用PJ 34作为化学工具来探测高微摩尔浓度下PARP 1和PARP 2的生物学作用的适当性应用于大多数研究。
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.