TABLE 1

Successful examples of applications of quantitative proteomics for characterization of in vitro ADME models

OrganStudy ObjectiveTarget DMET Protein QuantifiedReference
LiverEffect of pregnancy related hormones on protein abundance of UGTs in primary human hepatocytesUGTA1 and UGT2B7Khatri et al., 2021
Hepatocyte model selection to predict the uptake and biliary efflux of drugs in suspended, plated, and sandwich-cultured human hepatocytesOATP1B1, NTCP, MRP3, and BSEPKumar et al., 2019
Characterization of HepG2 3D spheroid model for hepatotoxicityCYPs, UGTs, GSTs, MRP1, and MRP4Hurrell et al., 2019
Comparison of protein abundance between human liver microsomes and hepatic cell lines (e.g., HepG2, Hep3B, and Huh7)CYPs, UGTs, SULTs, AKRs, GSTs, ALDHs, ADHs, AO, CESs, PONs, and EPXsShi et al., 2018a
Comparative proteomics analysis of HLM and HLS9 fractions for in vitro drug metabolism studiesCYPs, UGTs, SULTs, AKRs, GSTs, ALDHs, ADHs, AO, CESs, PONs, and EPXsWang et al., 2020
Effect of pregnancy-related hormones and induction of CYP3A activity over the course of pregnancy in HepaRG and SCHHs cellsCYP3AZhang et al., 2015b
Test primary hepatocytes as a suitable model for hepatic drug metabolism studyCYPs, UGTs, MDR1, MRPs, BCRP, NCP, OCTs, OATPs, CNTa, ENT1, and ATE1Schaefer et al., 2012
Interindividual variability in DMEs in HLMsCYPs and UGTsOhtsuki et al., 2012
Compare protein abundance between hepatic cell lines (HepG2, Hep3B, and Huh7)CYPs, UGTs, and ALDHsShi et al., 2018a
IntestineDrug metabolizing capabilities of human primary intestinal monolayersCYP3A4, UGT1A1, UGT1A10, UGT2B17, and CES2Speer et al., 2019
Effect of culture duration on transporter abundance in Caco-2 cellsMDR1, BCRP, PEPT1, OSTα and OSTβ, MRP2, MRP4, OATP2B1 and MCT1Uchida et al., 2015
Regional DMEs protein changes along the line of the small intestine using cryopreserved human intestinal mucosa (CHIM) modelUGTs, CESs, and SULTsZhang et al., 2020a
BrainDetermine the protein abundance of transporters and receptors in human brain microvesselsBCRP and P-gpUchida et al., 2011
Protein abundance of key membrane proteins in hCMEC/D3 cells and human brain microvesselsABCA2, MDR1, MRP4, BCRP, GLUT1, 4F2hc, MCT1, and ENT1Ohtsuki et al., 2013
Identify DMET protein expression in brain microvascular endothelial cellsGLUT1, EAAT1, EAAT2, BCRP, MDR1, CYP1B1, CYP2U1, GSTP1, COMT, GSTM3, GSTO1, and GSTM2Shawahna et al., 2011
Quantification of brain transporter abundance in brain microvascular endothelial cellsBCRP, P-gp, OATP2B1, ENT1, and GLUT1Billington et al., 2019
SkinCharacterization of in vitro models of human skinCYPs, ADHs, ALDHs, AKRs, AO, CESs, EPHx, and PONsCouto et al., 2021
Eye (retina)Transporter protein abundance in the plasma membranes of the human retinal pigment epithelium cells and immortalized arpe19 cell line)MRP1, MRP5, GLUT1, 4F2hc, TAUT, CAT1, LAT1, MPR7, OAT2, MCT1, MCT4, MRP4, RFC1, and MATE1Pelkonen et al., 2017