A novel ROCK inhibitor: off-target effects of metformin
In drug discovery, most small molecules cannot cross many stages, only a few can become drug candidates. Once the drug molecule is approved and marketed, nontarget effects that are not easily distinguishable from the actual target of the drugs might be evaluated. This situation restricts the treatment. Thus, the discovery of new drugs is a very long and expensive process. In recent years, without developing new drugs, the approach of using different and new target molecules in new indications apart from the indications of licensed drug molecules has gained importance. In this study, using the connectivity map program, it was determined that metformin and tolbutamide used in the treatment of type II diabetes had the potential to inhibit Rho kinase. In the experimental results to confirm this data, it has been shown that metformin and tolbutamide decrease the cell area within 24 h and metformin inhibits the activation of Rho kinase in MCF-7 cells. These results indicate that metformin, which is used in the treatment of type II diabetes, acts as a ROCK inhibitor. Metformin has potential in the treatment of various pathological conditions in which Rho kinase has a role.
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