In silico identification and in vivo characterization of small molecule therapeutic hypothermia mimetics.,Bioorganic & Medicinal Chemistry

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In silico identification and in vivo characterization of small molecule therapeutic hypothermia mimetics.
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2017-10-31 , DOI: 10.1016/j.bmc.2017.10.039
Claire Coderch ₁ , María Díaz de Cerio ₂ , Jose María Zapico ₁ , Rafael Peláez ₂ , Ignacio M Larrayoz ₂ , Ana Ramos ₁ , Alfredo Martínez ₂ , Beatriz de Pascual-Teresa ₁

Affiliation

Hypothermia has been proved to have a beneficial effect on several pathologies. CIRBP is one of the so termed cold-shock proteins involved in this process. In this work, we have detected small molecules capable of modulating the activity of CIRBP in the absence of a cold stimulus, by High Throughput Virtual Screening (HTVS) of the Diversity Set IV of the NCI and 15 compounds of our in-house data base. Fifteen compounds were selected from the HTVS to carry out a second screening through a cell-based Western blot assay. This assay, together with molecular modeling studies allowed us to select compound zr17-2 for an in vivo experiment, which showed an interesting increase of CIRBP expression in several organs of experimental animals. Therefore, we have demonstrated that the effect of hypothermia can be mimicked by small molecules, which can be developed as first-in-class new drugs for the treatment of several diseases.

中文翻译：

小分子模拟低温治疗的计算机识别和体内表征。

体温过低已被证明对几种病理都有有益的影响。CIRBP是参与此过程的所谓冷冲击蛋白之一。在这项工作中，我们通过NCI多样性集IV的高通量虚拟筛选（HTVS）和我们内部数据库的15种化合物，检测到了在不存在冷刺激的情况下能够调节CIRBP活性的小分子。。从HTVS中选择了15种化合物，以通过基于细胞的Western blot分析进行第二次筛选。该测定法和分子建模研究一起使我们能够选择化合物zr17-2进行体内实验，该实验显示了在实验动物的多个器官中CIRBP表达的有趣增加。因此，我们证明了低温可以通过小分子来模仿，

更新日期：2017-10-31

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