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Prasad Lab

Proteomics-based Research Initiative for Non-Cytochrome P450 Enzymes (PRINCE)

 

The Proteomics-based Research Initiative for Non-Cytochrome P450 Enzymes (PRINCE) is a research collaboration between Washington State University and multiple pharmaceutical companies. The overarching objective of PRINCE is to enable prediction of drug metabolism mediated by non-cytochrome P450 (non-CYP) enzymes. The research utilizes quantitative mass spectrometry proteomics for:

  • The characterization of differential tissue expression, interindividual variability, and inter-species differences in non-CYP enzymes
  • In vitro to in vivo extrapolation (IVIVE) of non-CYP metabolism for predicting drug clearance and fractional contribution of individual enzymes
  • Physiologically-based pharmacokinetic (PBPK) modeling of drugs metabolized by non-CYP enzymes

Specific aims and publications from PRINCE work:

PRINCE 1.0 (2018-19)

  • Characterization of differential tissue abundance of UDP glucuronosyltransferases (UGTs), aldehyde oxidase (AOX), and carboxylesterases (CESs) in human liver, intestine, kidney, heart, and lung (PMID: 32955894).
  • Regional proteomic quantification of clinically relevant non-cytochrome P450 enzymes along the human small intestine (PMID: 32350063).

PRINCE 2.0 (2019-21)

  • Protein abundance of non-cytochrome P450 drug-metabolizing enzymes across tissues in laboratory animal species (rat, mouse, dog, and monkey) versus humans (PMID: 34969659).

PRINCE 3.0 (2021-23)

  • Compare relative expression and relative activity factors (REF versus RAF) of human aldehyde oxidase (AO) and carboxylesterase (CES) in commercially available recombinant models and pooled tissue fractions (PMID: 37429730).
  • Ontogeny of AO in human liver cytosol and human hepatocytes
  • Develop PBPK models for predicting pharmacokinetics of AO and CES substates

PRINCE 4.0 (2023-25)

  • Validate global proteomics-based Total Protein Approach (TPA) for quantification of selected hydrolytic drug metabolizing enzymes (H-DMEs): Comparison of targeted versus TPA methods
  • Characterize ontogeny of H-DMEs in human hepatocytes
  • Quantify differential tissue abundance of H-DMEs in human
  • Quantify inter-species differences in H-DMEs (species: mouse, rat, dog, monkey, and human)

Consortium members:

  •  CORE members: The core members contribute in designing PRINCE research direction, continuous intellectual input in research, and manuscript writing.
  1. AbbVie
  2. Boehringer Ingelheim
  3. Genentech
  4. Gilead
  5. Takeda
  6. Merck (past member)
  • SUPPORTING member: The supporting members support PRINCE research by providing critical reagents or separate research funding on specific non-CYP research
  1. BioIVT
  2. IVAL
  3. Novartis
  4. Pfizer
  • ADVISORY Members: Individuals from industry or academia with interest to intellectually contributing to the non-CYP research conducted by PRINCE consortium

Membership benefits: 

Benefits to CORE members:
  • Vote for future directions of PRINCE research
  • Access to pre-publication data from the PRINCE research
  • Submission of up to 10 samples/per funding cycle for proteomics analysis of selected DMEs and transporter proteins
  • Participation in regular PRINCE teleconferences and face-to-face meetings
  • Opportunity to contribute as coauthors in manuscripts from PRINCE research
Benefits to SUPPORTING members:
  • Opportunity to contribute as coauthors in manuscripts from PRINCE research
Benefits to ADVISORY members:
  • Opportunity to participate in PRINCE research (co-authorship to be decided on case-by-case basis)

People: 

Program Director:

Bhagwat Prasad, Ph.D.

Research Team:
Contact:

Please contact Bhagwat Prasad if you are interested in becoming a PRINCE member or have any questions regarding this program.