TABLE 1.

Ligands and biological targets of NR1I3 (CAR) and NR1I2 (PXR)

Nuclear receptor	NR1I3 (CAR)		(NR1I2) PXR		Reference
Species	Rodent	Human a	Rodent	Human a
Ligands
Selective agonists	TCPOBOP, phenobarbital	CITCO, phenobarbital	PCN	Rifampicin Hyperforin SR12813	(Jimenez, Quattrochi, Yockey, & Guzelian, 2000; Jones et al., 2000; Kliewer et al., 1998; Moore et al., 2000; Tzameli, Pissios, Schuetz, & Moore, 2000)
Antagonists	https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2760	CINPA‐1 https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2757	https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2568	Ketoconazole, l‐https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6569, coumestrol, SPA70	(Cherian et al., 2018; Forman et al., 1998; Huang et al., 2007; Lemmen, Tozakidis, Bele, & Galla, 2013; Lin et al., 2017; Wang et al., 2008; Yeung, Sueyoshi, Negishi, & Chang, 2008)
Biological targets
Enzymes
CYP450 isoforms	Cyp1a1, Cyp1a2, Cyp2a4, Cyp2b10, Cyp2c29, Cyp2c37, Cyp2c55, Cyp3a11	CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5	Cyp3a, Cyp3a11, Cyp2b9, Cyp2b10, Cyp2c55	CYP3A4, CYP3A23, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP1A	(Aleksunes & Klaassen, 2012; Chen, Ferguson, Negishi, & Goldstein, 2003; Ferguson, Chen, LeCluyse, Negishi, & Goldstein, 2005; Ferguson, LeCluyse, Negishi, & Goldstein, 2002; Goodwin, Hodgson, D'Costa, Robertson, & Liddle, 2002; Maglich et al., 2004; Xu, Wang, & Staudinger, 2009; Yoshinari, Yoda, Toriyabe, & Yamazoe, 2010; Zhang, Huang, Chua, Wei, & Moore, 2002)
UGTs	Ugt1a1, Ugt1a9, Ugt2b34, Ugt2b35, Ugt2b36	UGT1A1	Ugt1a1, Ugt1a5, Ugt1a9	UGT1A1, UGT1A6, UGT1A3, UGT1A4	(Aleksunes & Klaassen, 2012; Maglich et al., 2004; Sugatani et al., 2005)
Sulfotransferases	Sult1a1, Sult1d1, Sult1e1, Sult2a1, Sult2a2, Sult3a1, Sult5a1	SULT2A1	Sult1a1, Sult1e1, Sult2a1, Sult2a2, Sult5a1	SULT2A1	(Aleksunes & Klaassen, 2012; Alnouti & Klaassen, 2008; Chen, Zhang, Baker, & Chen, 2007; Echchgadda et al., 2007; Maglich et al., 2004)
GSH‐S‐transferases	Gsta1, Gsta3, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Gstp, Gstt1, Gstt3		Gsta1, Gsta3, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Gstm6, Gstp, Gstt1, MGst1	GSTA1, GSTA2, GSTM1, GSTP1‐1	(Aleksunes & Klaassen, 2012; Cui, Choudhuri, Knight, & Klaassen, 2010; Knight, Choudhuri, & Klaassen, 2008; Singh et al., 2012; Zhang et al., 2002)
Gluconeogenic enzymes	PEPCK, G6P‐ase		PEPCK, G6P‐ase	PEPCK, G6P‐ase	(Kodama, Koike, Negishi, & Yamamoto, 2004; Kodama, Moore, Yamamoto, & Negishi, 2007; Mackowiak et al., 2019)
Lipogenic enzymes	Scd‐1		Scd‐1	SCD‐1	(Nakamura, Moore, Negishi, & Sueyoshi, 2007; Zhang et al., 2013)
β‐oxidation‐related enzymes	Cpt1a		Cpt1a	CPT1A	(He et al., 2013; Moreau et al., 2009; Nakamura et al., 2007; Ueda et al., 2002)
Ketogenic enzymes	Hmgcs2		Hmgcs2		(Gao, He, Zhai, Wada, & Xie, 2009; He et al., 2013)
Transporters
ABC	P‐gp, Bcrp, Mrp2, Mrp4	P‐GP, BCRP, MRP2	P‐gp, Bcrp, Mrp2, Mrp4	P‐GP , BCRP, MRP2, ABCBA1, ABCG1	(Bauer, Hartz, Fricker, & Miller, 2004; Kast et al., 2002; Lemmen, Tozakidis, Bele, & Galla, 2013; Lemmen, Tozakidis, & Galla, 2013; Martin et al., 2008; Narang et al., 2008; Oswald et al., 2006; Ott et al., 2009; Petrick & Klaassen, 2007; Teng & Piquette‐Miller, 2005; Wang, Sykes, & Miller, 2010; Whyte‐Allman, Hoque, Jenabian, Routy, & Bendayan, 2017; Yamasaki, Kobayashi, & Chiba, 2018)
SLC	https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=165#876, https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=238#1219			https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=238#1219, https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=238#1219	(Aleksunes & Klaassen, 2012; Hassani‐Nezhad‐Gashti et al., 2018; Li et al., 2015; Meyer zu Schwabedissen, Tirona, Yip, Ho, & Kim, 2008)

^aStudies performed in higher mammalian models including porcine are included since ligands for human NR1I3 (CAR) and NR1I2 (PXR) also activate these orthologues.