1. Genetic Polymorphism (Asian) CYP2D6 SNP C188T (70%T) CYP2A6*4 (27%) CYP3A5*3 (72%) OATP2 SNP A388G (78%G) MRP1 SNP C218T (1%T), G2168A (2%A) MRP2 SNP G1249A (7%A), C2366T (1%T)

2. Nuclear Proteins Nuclear orphan receptors Transcriptional factors

3. Nuclear Orphan Receptors PPAR  : ligand- fibrates, lower blood lipid PPARγ: ligand- traglitazone etc., lower blood sugar in NIDDM PPARδ, LXRα, LXRβ PXR: ligand- rifampin etc., induce CYP3A4, and P-glycoprotein CAR: ligand- phenobarbital, induce CYP2B6 and other genes

4. -2723 Sp1 c-Myb AP2 GATA-1 IRF-2c-MycAP1 c-Ets-1/PEA3 HiNF-APit-1CCAATHNF-1CREBNF-E C/EBP  COUP Transcriptional regulatory elements in Mrp3 promoter -19 NF-1

5. Sp1 Sp3 L1 L2 L3 L4 H I I1 I2 C/EBP  C/EBP  LAP-FL LAP LIP C/EBP  LiverIntestine Tissue Distribution of Sp1/Sp3 and C/EBP protein family  C/EBP  as a inducible factor, shows no constitutive expression in liver and hepatoma cell lines (H, H4IIE).

6. Proteomics in Drug Development and Review Xenobiotic affects transcriptional factors Example xenobiotic A → C/EBP → MRP3 → clearance of substrates drug-drug interaction study proteomic design, for example, xenobiotic A and MRP3 substrates