Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Proteins are the primary targets of almost all small molecule drugs.
However, even the most selectively designed drugs can potentially target several unknown proteins. Identification of potential drug targets can facilitate design of new drugs and repurposing of existing ones.
Current state-of-the-art proteomics methodologies enable screening of thousands of proteins against a limited number of drug molecules. Here we report the development of a label-free quantitative proteomics approach that enables proteome-wide screening of small organic molecules in a scalable, reproducible, and rapid manner by streamlining the proteome integral solubility alteration PISA assay.
We used rat organs ex-vivo to determine organ specific targets of medical drugs and enzyme inhibitors to identify drug targets for common drugs such as Ibuprofen.
Finally, global drug profiling revealed overarching trends of how small molecules affect the proteome through either direct or indirect protein interactions. The primary objective in small molecule drug design is to maximize the potency and specificity towards the target protein. This ensures that the desired pharmacological effects through hypothesized mechanisms of action MoAs are achieved while minimizing the risk of off-target interactions that can lead to unforeseen and undesirable side effects.
