Andrew Shum; Northwestern University
Richard J. Miller; Northwestern University
Biochemistry, Biophysics, and Structural Biology | Cancer Biology | Cell and Developmental Biology | Cell Biology | Immunity | Immunology and Infectious Disease | Life Sciences | Molecular Biology
CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in calcium concentration in the cell due to CXCR4 activation. There was an increase in calcium in the cells when 390 was added, indicating that the receptor was being activated. When compared to the natural ligand, SDF-1, the levels were not as high, but they were higher than with the vehicle control. In the internalization assay, both SDF-1 and 390 internalized the receptor. The results suggest 390 is an agonist or partial agonist of the CXCR4 receptor. 390 may be the first small molecule agonist of CXCR4 receptors ever identified and may have a number of uses in medicine.
Zenebe-Gete, S. B., Topudurti, S. R., Shum, A., & Miller, R. J. (2014). The effect of small molecule 390 on CXCR4 receptors. Young Scientist: A High School Research Journal, 4, 66-68. Retrieved from http://digitalcommons.imsa.edu/student_pr/11/