Gentile, Francesco Deriu, Marco A. Barakat, Khaled Danani, Andrea Tuszynski, Jack 2018-02-16 The 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. application/pdf https://n2t.net/ark:/12658/srd1319108 https://susi.usi.ch/global/documents/319108 https://susi.usi.ch/documents/319108/files/Gentile_P_2018.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.3390/ph11010022 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319108 info:eu-repo/semantics/openAccess CC BY Pharmaceuticals. - 2018, vol. 11, no. 1, p. 22 TLR7 Colchicine Imiquimod Innate immune system Off-target interaction info:eu-repo/classification/udc/57 A novel interaction between the TLR7 and a colchicine derivative revealed through a computational and experimental study http://purl.org/coar/resource_type/c_6501