2. Academic Validation
  3. In silico identification and in vivo characterization of small molecule therapeutic hypothermia mimetics

In silico identification and in vivo characterization of small molecule therapeutic hypothermia mimetics

  • Bioorg Med Chem. 2017 Dec 15;25(24):6597-6604. 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 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain.
  • 2 Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
  • 3 Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain. Electronic address: [email protected].
PMID: 29137939 DOI: 10.1016/j.bmc.2017.10.039
Abstract

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.

Keywords

CIRBP; Cold-shock protein; HTVS; Hypothermia mimetics; Molecular modeling.

Figures
Products