Table 1.

List of formal NRs and atypical receptor-like proteins known to be involved in drug-metabolism gene regulation.

Formal NRs involved in drug metabolism and disposition
NR	Major gene types regulated	Effects upon induction	Key ligands and types
PXR	CYPs, UGTs, GST, SULTs, MDR, MRP, OATs	Detoxification and biotransformation of xenobiotics, regulation of homeostasis	Various drug, drug-like, and endobiotic compounds
CAR	CYPs, UGTs, GST, SULTs, MDR, MRP, OATs	Detoxification and biotransformation of xenobiotics, regulation of homeostasis	Small-molecule compounds
FXRa	CYPs, UGTs, SULTs, MRP, OATs, MDR, SHP, PPAR, PXR	Bile acid and lipid homeostasis, bile acid export and regulation of bile acid formation	Cholesterol-based compounds, farnesol metabolites, bile acid metabolites
VDR	CYPs, SULTs, MRP, FXR	Calcium homeostasis, cell proliferation and differentiation	1α,25-dihydroxyvitamin D3, LCA
HNF4αb	CYPs, SULTs, MDR, OATs, PXR, CAR, PPAR, FXR	Liver development, lipid and bile metabolism, bile acid synthesis	Fatty acids, linoleic acid
PPAR	CYPs, UGTs, GSTs, SULTs, MDR, FXR, SHP	Fatty acid homeostasis, repression of bile acid synthesis, inflammation	Fatty acids, thiazolidinediones, hypolipidemic fibrates
GRb	CYPs, MRP, CAR, PXR, RXRα	Immunoresponse, stimulation of bile acid transport	Glucocorticoids
LXR	SULTs	Regulation of cholesterol synthesis and absorption, modulation of bile acid toxicity and cholestasis	Cholesterol-based compounds (oxysterols)
RORb	CYPs, SULTs, GSTs	Triglyceride regulation, glucose homeostasis	Cholesterol, retinoic acids, melatonin, thiazolidindiones
RXR	Dependent on binding Partner	Dependent on binding partner	Retinoic acids

Atypical NR-like proteins involved in drug metabolism and disposition
Receptor	Major genes regulated	Effects upon induction	Key ligands and types
AhR	CYPs, GSTs, UGTs, MRP, SULTs	Cell-cycle control, metabolic adaptation to xenobiotics, chemical toxicity signals	Polycyclic aromatic hydrocarbons, halogenated aromatic hydrocarbons
SHP	AR, ER, HNF4, LRH-1, LXR, PPAR, RAR, RXR, and other NRs	Repression of NRs through heterodimerization	Small, synthetic molecules, others unknown
Nrf2	GSTs, UGTs, SULTs, MRP, AhR	Protection against oxidative and electrophilic stress	—

Detailed for each NR (top) are the major gene types regulated, the observed effects upon receptor activation, and some of the known ligands and ligand types. Further outlined are atypical and receptor-like proteins (bottom) that have been identified as modulators of drug metabolism and formal NRs with direct effects on gene regulation. For these informal receptors, the major genes and proteins regulated, the observed effects, and key ligand types are given.

^aCan function with or without RXRα.

^bFunctions as monomer or homodimer.