The Proteomics-based Research Initiative for Non-CYP Enzymes (PRINCE) is a research collaboration between Washington State University and the pharmaceutical industry
To enable prediction of non-CYP metabolism of xeno- and endobiotics by generating quantitative physiological data on:
- Differential tissue expression (hepatic and extra-hepatic metabolism)
- Variability: Effect of age, sex, race, genetics, etc.
- Inter-species differences
Challenges in predicting non-CYP metabolism
Year 1 (2018-19)
Aim 1: To characterize differential tissue abundance (using quantitative proteomics) of non-CYP enzymes including UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, UGT2B15, UGT2B17, UGT2B4, AO, CES1 and CES2 in human intestine, kidney, heart, lung and liver by LC-MS/MS
Aim 2: To characterize intestinal abundance of above non-CYP enzymes in cryopreserved human intestinal mucosa (CHIM) model
Aim 3: To select animal species for year 3 and preliminary method development for quantification of non-CYP enzymes in pre-clinical species
Year 2 (2019-20)
Aim 1: LC-MS/MS method development for quantification of non-CYP enzymes in pre-clinical species
Aim 2: Interspecies quantification of non-CYP DMEs and application to IVIVE in drug disposition related tissues
Please contact Bhagwat Prasad if you are interested to become a PRINCE member or have any questions regarding this program.