We have developed, or have conceptual designs, for chemical probes to cover the mammalian enzyme families associated with phase 1 (oxidation) and phase 2 (conjugation) drug and xenobiotic metabolism. Our activity-based probes enable the selective characterization of any functionally active isoforms of enzymes within the superfamilies of enzymes that perform phase 1 and 2 metabolism. Specifically, these probes don't provide a readout of the total activity of an enzyme family, but instead provide the activity contribution of individual enzymes. This goes well beyond anything that is commercially available, which primarily measure total enzyme family activities. Specifically we have developed chemical probes for cytochrome P450 enzymes (phase 1), glutathione S-transferases (phase 2), epoxide hydrolases (phase 2), UDP-glucuronosyltransferases (UGTs; phase 2), sulfotransferases (phase 2), and we have conceptual designs for aldoketoreductases and NAD(P)H quinone oxidoreductases (both phase 2). See attached file on phase 1 and 2 drug metabolism. All of the chemical probes enable multimodal profiling, meaning measurements can be made by imaging, flow cytometry, and proteomics. We are currently working on ways to immobilize the probes on to glass or other resin surfaces, such that arrays of probes can be rapidly developed to broadly characterize mammalian metabolism in organ tissues and extracts (e.g. liver), or cell lines and extracts. The arrays we are developing will enable two primary measurements: (1) we will be able to rapidly profile which enzymes are involved in the metabolism of a drug or xenobiotic (e.g., a pesticide); (2) we will be able to rapidly determine the specific phase 1/2 enzymes that are inhibited or activated by a drug or xenobiotic. Important note: the probes for cytochrome P450s were originally developed and published when Aaron Wright was a postdoc at the Scripps Research Institute. They were not patented at that point. We have since published with these probes in other programs at PNNL. However, there is no publication that discusses their use in arrays for rapid characterization of metabolism or inhibition/activation by a drug or xenobiotic.