TABLE 3

Compounds considered as in vivo human BCRP substrates based on available in vitro data

Metabolites are listed below the respective parent compound. K_m and efflux ratio values are presented as reported in the respective references.

Object	Object Therapeutic Class	Experimental System	Efflux Ratio^{^a}	K_m	Reference(s)
				μM
(−)-Pantoprazole	Proton pump inhibitors	MDCK-transfected cells		0.59	Wang et al., 2012
(+)-Pantoprazole	Proton pump inhibitors	MDCK-transfected cells		5.32	Wang et al., 2012
2′-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		5.4	Wei et al., 2013
3,2′-Dihydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		35.9	Wei et al., 2013
3,3′-Dihydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		45.2	Wei et al., 2013
3,4′-Dihydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		35.9	Wei et al., 2013
3,5-Dihydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		12.8	Wei et al., 2013
3,5-Di-O-caffeoylquinic acid	Food products	Caco-2 cells	5.1		Farrell et al., 2012
3,6-Dihydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		31.9	Wei et al., 2013
3,7-Dihydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		3.5	Wei et al., 2013
3′-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		5.6	Wei et al., 2013
3-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		9.7	Wei et al., 2013
4-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		17.5	Wei et al., 2013
5-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		48.5	Wei et al., 2013
6-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		26.8	Wei et al., 2013
7-Hydroxyflavone-O-glucuronide	Food products	HeLa-transfected cells		9	Wei et al., 2013
Aconitine	Herbal medications	MDCK-transfected cells	19.8		Ye et al., 2013
Apixaban	Anticoagulants and antiplatelets	MDCK-transfected cells	12		Zhang et al., 2013
Axitinib	Kinase inhibitors	MDCK-transfected cells	3.4		http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202324Orig1s000TOC.cfm
Barasertib hydroxy-QPA	Kinase inhibitors	MDCK-transfected cells	2.31		Marchetti et al., 2013
Boceprevir	Antivirals	MDCK-transfected cells	2		Chu et al., 2013a
Bupropion	Dopamine-norepinephrine reuptake inhibitors	Membrane vesicles		3	Hemauer et al., 2010
Canertinib	Kinase inhibitors	MDCK-transfected cells	2.8		Xiao et al., 2006
Chlorothiazide	Diuretics	MDCK-transfected cells	36		Beery et al., 2012
Cimetidine	H2 receptor antagonists	MDCK-transfected cells	3.4		Pavek et al., 2005
Ciprofloxacin	Antibiotics	MDCK-transfected cells	2.9		Merino et al., 2006
Dantrolene	Muscle relaxants	Caco-2 cells	5		Xiao et al., 2012
Daunorubicin	Anthracyclines	Caco-2 cells	4.9		Lin et al., 2011
Dimenhydrinate	H1 receptor antagonists	Caco-2 cells	9.8		Crowe and Wright, 2012
Dipyridamole	Anticoagulants and antiplatelets	MDCK-transfected cells	2.7		Zhang et al., 2005b
Dolutegravir	HIV integrase strand transfer inhibitors	MDCK-transfected cells	3.1		Reese et al., 2013
Edaravone sulfate	Neuroprotectors	Membrane vesicles		16.5	Mizuno et al., 2007
Erythromycin	Antibiotics	Caco-2 cells	8.1		Lin et al., 2011
Estradiol-17-β-glucuronide	Estrogens	Membrane vesicles		44.2	Chen et al., 2003
Estrone-3-sulfate	Estrogens	Caco-2 cells	48.5 (Li)	6.8^{^b} (Imai)	Imai et al., 2003; Li et al., 2011a
Ethinyl estradiol sulfate	Estrogens	Membrane vesicles		2.9	Han et al., 2010
Etoposide	Topoisomerase inhibitors	Caco-2 cells	12.7		Lin et al., 2011
Flavopiridol (alvocidib)	Kinase inhibitors	MDCK-transfected cells	6		Zhou et al., 2009
Fluvastatin	HMG-CoA reductase inhibitors (statins)	Caco-2 cells	4.9		Lin et al., 2011
Furosemide	Diuretics	Caco-2 cells	17.5		Lin et al., 2011
Gemifloxacin	Antibiotics	MDCK-transfected cells		145.69	Jin et al., 2013
Genistein	Food products	LLC-PK1-transfected cells	2		Imai et al., 2004
Glyburide (glibenclamide)	Sulfonylureas	MDCK-transfected cells	9.3 (Varma)	13.07^{^c} (Pollex)	Pollex et al., 2010; Varma et al., 2014
Grepafloxacin	Antibiotics	MDCK-transfected cells	9.14		Ando et al., 2007
Hematoporphyrin	Photosensitizing agents	Membrane vesicles		17.8	Tamura et al., 2006
Hypaconitine	Herbal medications	MDCK-transfected cells	7.6		Ye et al., 2013
Imatinib	Kinase inhibitors	MDCK-transfected cells	2.4		Zhou et al., 2009
Irinotecan	Topoisomerase inhibitors	Caco-2 cells	3.7		Lin et al., 2011
SN-38	Topoisomerase inhibitors	MDCK-transfected cells	8.4	4^{^b}	Nakatomi et al., 2001; Xiao et al., 2006
SN-38 glucuronide	Topoisomerase inhibitors	Membrane vesicles		26	Nakatomi et al., 2001
Lamivudine	Nucleoside reverse transcriptase inhibitors	MDCK-transfected cells	3	216.5	Kim et al., 2007
Lapatinib	Kinase inhibitors	MDCK-transfected cells	2.6		Polli et al., 2008
Mesaconitine	Herbal medications	MDCK-transfected cells	11.		Ye et al., 2013
Methotrexate	Antimetabolites	MDCK-transfected cells	6.78 (Xia)	681^{^b} (Volk and Schneider)	Volk and Schneider, 2003; Xia et al., 2007
Mitoxantrone	Other antineoplastics	MDCK-transfected cells	6.1		Xiao et al., 2006
Nitrofurantoin	Anti-infective agents	Caco-2 cells	24.1 (Lin)	69.4 (Wright)	Lin et al., 2011; Wright et al., 2011
Norfloxacin	Antibiotics	Caco-2 cells	3		Lin et al., 2011
Olomoucine II	Kinase inhibitors	MDCK-transfected cells	2.27		Hofman et al., 2013
Pemetrexed	Antimetabolites	Membrane vesicles		390	Li et al., 2011b
Pitavastatin	HMG-CoA reductase inhibitors (statins)	Membrane vesicles		5.73	Hirano et al., 2005
Prazosin	α/β-adrenergic antagonists	MDCK-transfected cells	11.1		Li et al., 2012
Rivaroxaban	Anticoagulants and antiplatelets	Caco-2 cells	2.82		Gong et al., 2013
Rosuvastatin	HMG-CoA reductase inhibitors (statins)	Caco-2 cells	83.2	2.02^{^b}	Kitamura et al., 2008; Li et al., 2012
Sildenafil	Erectile dysfunction treatments	MDCK-transfected cells	3.59	22.4	Choi and Song, 2012
Sorafenib	Kinase inhibitors	MDCK-transfected cells	2.7		Lagas et al., 2010
Sulfasalazine	Nonsteroidal anti-inflammatory drugs	Caco-2 cells	87 (Wang)	0.7^{^b} (Jani)	Wang et al., 2008; Jani et al., 2009
Sunitinib	Kinase inhibitors	MDCK-transfected cells	1.9^{^d}		Tang et al., 2012a
N-Desethyl sunitinib (SU12662)	Kinase inhibitors	MDCK-transfected cells	13.5		Tang et al., 2012b
Tandutinib	Kinase inhibitors	Caco-2 cells	5	4	Yang et al., 2010
Temocapril	Angiotensin-converting enzyme inhibitors	Caco-2 cells	5.56		Ohura et al., 2011
Teniposide	Topoisomerase inhibitors	Caco-2 cells	10.8		Lin et al., 2011
Teriflunomide	Other immunomodulators	Caco-2 cells	9.37		http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202992Orig1s000TOC.cfm
Topotecan	Topoisomerase inhibitors	Caco-2 cells	13.1	213.28^{^e} Li	Li et al., 2008; Lin et al., 2011
Troglitazone sulfate	Thiazolidinediones	MDCK-transfected cells	6.42		Enokizono et al., 2007a
Ulifloxacin	Antibiotics	MDCK-transfected cells	2.95		Ando et al., 2007
Vardenafil	Erectile dysfunction treatments	MDCK-transfected cells	4.12	14.3	Choi and Song, 2012

↵^a Compounds with efflux ratios of >2 were selected for further consideration.
↵^b Kinetic experiments were performed in membrane vesicles.
↵^c Kinetic experiments were performed in HEK-transfected cells.
↵^d Included in the list because metabolite has an efflux ratio of >2.
↵^e Kinetic experiments were performed in MDCK-transfected cells.