. 2021 Apr;73(2):847–859. doi: 10.1124/pharmrev.120.000106

TABLE 2.

Recommended enzymes, transporters, and experimental systems for screening natural products for inhibition and/or induction

Adapted with permission from the American Society for Pharmacology and Experimental Therapeutics from Johnson et al. (2018).

Cytochrome P450 enzymes
Essential: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A
Experimental System	Inhibition	Induction
Recombinant enzymes	As needed	NA
Human liver microsomes	^a	NA
Human hepatocytes	As needed	^a
Human intestinal microsomes	As needed	NA
Human intestinal cells	As needed	As needed^b
Human kidney microsomes	As needed	NA
Human kidney cells	As needed	As needed^b
Other cell lines	As needed	NA

UGTs
Essential: UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, UGT2B10, UGT2B15
Experimental System	Inhibition	Induction
Recombinant enzymes	As needed	NA
Human liver microsomes	^a	NA
Human hepatocytes	^a	^a
Human intestinal microsomes	As needed	NA
Human intestinal cells	As needed	As needed^b
Human kidney microsomes	As needed	NA
Human kidney cells	As needed	As needed^b
Other cell lines	As needed	NA

Other Enzymes that May Be Considered
hCE1, hCE2, SULT1A1, SULT1A3, SULT1B1, SULT1E1, SULT2A1
Experimental System	Inhibition	Induction
Recombinant enzymes	^a	NA
Human liver microsomes	^a	NA
Human hepatocytes	As needed	^a
Human intestinal microsomes	As needed	NA
Human intestinal cells	As needed^b	As needed^b
Human kidney microsomes	As needed^b	NA
Human kidney cells	As needed^b	As needed^b

Transporters
Essential: BCRP, BSEP, MATE1, MATE2-K, MRP2, MRP3, NTCP, OATP1B1, OATP1B3, OATP2B1, OAT, OCT, P-gp
Experimental System	Inhibition	Induction
Transfected cell lines (single, double)	^a	NA
Human intestinal cells	As needed^b	As needed^b
Human kidney cells	As needed^b	As needed^b
Human hepatocytes	^a	^a
Membrane vesicles	^a	NA

BCRP, breast cancer resistance protein; BSEP, bile salt export pump; hCE, human carboxylesterase; MATE, multidrug and toxin extrusion protein; MRP, multidrug resistance–associated protein; NA, not applicable; NTCP, sodium taurocholate–cotransporting polypeptide; OAT, organic anion transporter; OATP, organic anion–transporting polypeptide; OCT, organic cation transporter; P-gp, P-glycoprotein; SULT, sulfotransferase.

^{^a}

Essential system. Inhibition studies in hepatocytes may involve multiple transporters.

^{^b}

These models represent an emerging field and will be refined with time. Expression levels of enzymes and transporters in these models are lower than those in vivo (Speer et al., 2019; Chapron et al., 2020; Kasendra et al., 2020).