A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study
AbstractThe Toll-Like Receptor 7 (TLR7) is an endosomal membrane receptor involved in the innate immune system response. Its best-known small molecule activators are imidazoquinoline derivatives such as imiquimod (R-837) and resiquimod (R-848). Recently, an interaction between R-837 and the colchicine binding site of tubulin was reported. To investigate the possibility of an interaction between structural analogues of colchicine and the TLR7, a recent computational model for the dimeric form of the TLR7 receptor was used to determine a possible interaction with a colchicine derivative called CR42-24, active as a tubulin polymerization inhibitor. The estimated values of the binding energy of this molecule with respect to the TLR7 receptor were comparable to the energies of known binders as reported in a previous study. The binding to the TLR7 was further assessed by introducing genetic transformations in the TLR7 gene in cancer cell lines and exposing them to the compound. A negative shift of the IC50 value in terms of cell growth was observed in cell lines carrying the mutated TLR7 gene. The reported study suggests a possible interaction between TLR7 and a colchicine derivative, which can be explored for rational design of new drugs acting on this receptor by using a colchicine scaffold for additional modifications. View Full-Text
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Gentile, F.; Deriu, M.A.; Barakat, K.; Danani, A.; Tuszynski, J. A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study. Pharmaceuticals 2018, 11, 22.
Gentile F, Deriu MA, Barakat K, Danani A, Tuszynski J. A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study. Pharmaceuticals. 2018; 11(1):22.Chicago/Turabian Style
Gentile, Francesco; Deriu, Marco A.; Barakat, Khaled; Danani, Andrea; Tuszynski, Jack. 2018. "A Novel Interaction Between the TLR7 and a Colchicine Derivative Revealed Through a Computational and Experimental Study." Pharmaceuticals 11, no. 1: 22.
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