TABLE 1

LXR-activating compounds

Overview of compounds that activate LXR, including their primary pharmacological action, effects on ABCA1 and ABCG1 expression (arrows: mRNA, protein), and effects on cellular cholesterol efflux. Effects on ABCA1, ABCG1, and cholesterol efflux are presented as follows: (↓) decreased; (= ) no effect; (↑) increased. Italicized symbols indicate changes in ABCA1 and ABCG1 mRNA levels, whereas nonitalicized symbols indicate protein levels.

Compound	Primary Action	ABCA1		ABCG1		Cholesterol Efflux		Reference
Acetyl-podocarpic dimer	Selective LXR agonist	↑	THP-1	↑	Caco-2		THP-1	Sparrow et al., 2002
		↑	Caco-2	↑	Primary hepatocytes^{^a}	↑	apoA-I
		↑	Primary hepatocytes^{^a}			↑	Caco-2
						↑	Monocytes^{^a}
							Primary fibroblasts^{^a}:
						↑	apoA-I
Baclofen	GABA_B receptor agonist		—		—		MDM	Yang et al., 2014
						=	apoA-I
						=	HDL
Digoxin	Na⁺-K⁺-ATPase inhibitor	↑	H9c2		—	↑	H9c2	Campia et al., 2012
Disodium ascorbyl phytostanol phosphate (FM-VP4)	MDR1 antagonist	↑	Liver^{^b}		—		—	Méndez-González et al., 2010
Disodium ascorbyl phytostanol phosphate (FM-VP4)	MDR1 antagonist	=	Small intestine^{^b}		—		—	Méndez-González et al., 2010
Daunorubicin	Anthracycline antibiotic	=	HL-1	=	HL-1		—	Monzel et al., 2017
DMHCA	LXRα agonist	↑	THP-1	↑	BREC	↑	THP-1	Quinet et al., 2004; Kratzer et al., 2009; Hammer et al., 2017
		↑	J774	↑	PM^{^c}
		↑	HepG2	↑	Liver^{^a}^,^{^d}
		↑↑	BREC	↑	Ileum^{^d}
		↑	PM^{^b}^,^{^c}	↑	Aorta^{^d}
		↑	Liver^{^a}
		=	Liver^{^d}
		↑	Ileum^{^d}
		↑	Aorta^{^d}
Doxorubicin	Anthracycline antibiotic	↑	HL-1	↑	HL-1		HL-1	Monzel et al., 2017
						↑	apoA-I
						↑	HDL
E17110	Benzofuran-2-carboxylate analog	↑↑	RAW264.7	↑↑	RAW264.7		RAW264.7	Li et al., 2016
						↑	apoA-I
						↑	HDL
(E)-1-(e,4-diisopropoxyphenyl)-3-(4-isopropoxy-3-methoxyphenyl-2-en-1-one	Chalcone derivative	↑↑	THP-1	↑	THP-1		—	Teng et al., 2018
Ergosterol derivatives	Ergosterol analog	↑	U937					Marinozzi et al., 2017
Etoposide	DNA topoisomerase II inhibitor	↑	RAW264.7	↑	PM^{^b}	↑	PM	Zhang et al., 2013a
		↑↑	PM^{^b}			↑	RCT^b
		↑	THP-1
			Blood monocyte^{^a}
EXEL-04286651/BMS-779788	LXR partial agonist	↑	Murine blood cells	↑	Murine blood cells		—	Kick et al., 2015; Kirchgessner et al., 2015
EXEL-04286651/BMS-779788	LXR partial agonist	↑	Murine blood cells	↑	Blood cells^{^e}		—	Kick et al., 2015; Kirchgessner et al., 2015
FTY720-P	Sphingosine-1-phosphate analog	↑	Monocytes^{^a}		—	↑	Monocytes^{^a}	Blom et al., 2010
G004	Unknown (synthetic sulfonylurea compound)	↑↑	RAW264.7	↑↑	RAW264.7	↑	RAW264.7	Qian et al., 2017
G004	Unknown (synthetic sulfonylurea compound)	↑	Liver^{^c}	↑↑	Liver^{^c}	↑	RCT^{^c}	Qian et al., 2017
GW3965	LXRα agonist	↑	THP-1	↑	haSMC^{^a}	↑	THP-1	Miao et al., 2004; Quinet et al., 2004, 2006; Brunham et al., 2006; Naik et al., 2006; Delvecchio et al., 2007; DiBlasio-Smith et al., 2008; Kannisto et al., 2014
		↑	J774	↑=	Liver^{^b}	↑	RCT^{^b}
		↑	HepG2	↑	Peripheral blood^{^f}
		↑	haSMC^{^a}	↑	Spleen^{^f}
		↑	BMM	↑	Prox small intestine^{^b}^,^{^g}
		↑	PM^{^b}^,^{^h}^,^ⁱ
		↑↑	Liver^{^a}^,^{^h}
		↑=	Liver^{^a}^,^{^h}
		↑	Peripheral blood^{^f}
		↑	Spleen^{^f}
		↑↑	Prox small intestine^{^b}
		=	Prox small intestine^{^g}
		↑	Kidney^{^b}^,^{^h}
		↑	Duodenum^{^b}^,^{^h}
Ibandronate	Osteoclast inhibitor	↑	MM6		—	↑	MM6	Strobach and Lorenz, 2003
Ibandronate	Osteoclast inhibitor	↑	PBMCs^{^a}		—	↑	MM6	Strobach and Lorenz, 2003
Ibrolipim (NO-1886)	Lipoprotein lipase activator	↑↑	THP-1	↑↑	THP-1	↑	THP-1	Zhang et al., 2006; Ma et al., 2009; Chen et al., 2010
		↑↑	Liver^{^j}
		↑↑	Adipose tissue^{^j}
		↑↑	Aorta^{^j}
Idarubicin	Anthracycline antibiotic	↑	HL-1	↑	HL-1			Monzel et al., 2017
IMB-151	Unknown	↑↑	RAW264.7	↑↑	RAW264.7	↑	RAW264.7	Li et al., 2014
Infliximab	Anti–TNF-α mAb	↑↑	THP-1	==	THP-1	↑	THP-1 (restores effect of TNF-α)	Voloshyna et al., 2014
Lansoprazole	Proton pump inhibitor	↑	H4 neuroglioma cells^{^a}		—		—	Cronican et al., 2010
		↑	U-87 astrocytoma
		↑↑	CCF astrocytoma
		↑	U-118 astrocytoma
		↑	Primary astrocytes^{^b}
LXR-623	Synthetic LXR agonist	↑	Duodenum^{^g}	↑	Duodenum^{^g}		—	DiBlasio-Smith et al., 2008; Katz et al., 2009; Quinet et al., 2009
		=	Liver^{^g}	=	Liver^{^g}
		↑	Spleen^{^f}	↑	Spleen^{^f}
		↑	Peripheral blood^{^a}^,^{^b}^,^{^f}	↑	Peripheral blood^{^a}^,^{^b}^,^{^f}
		↑↑	PBMCs^{^a}	↑↑	PBMCs^{^a}
		↑	Whole blood^{^a}^,^e	↑	Whole blood^{^a}^,^{^e}
Methyl-3β-hydroxy-5α,6α-epoxycholanate	LXRα agonist	↑	THP-1		—		—	Yan et al., 2010
Methyl-3β-hydroxy-5α,6α-epoxycholanate	LXRα agonist	↑	Aorta^{^c}		—		—	Yan et al., 2010
Omeprazole	Proton pump inhibitor	↑	H4 neuroglioma cells^{^a}		—		—	Cronican et al., 2010
Pantoprazole	Proton pump inhibitor	↑	H4 neuroglioma cell^{^a}		—		—	Cronican et al., 2010
Ouabain	Na⁺-K⁺-ATPase inhibitor	↑	H9c2		—	↑	H9c2	Campia et al., 2012
Ritonavir	Viral proteinase inhibitor	↑↑	THP-1	=	THP-1		—	Pou et al., 2008
Sirolimus	FK-binding protein-12 inhibitor	↑	hVSMC	=	hVSMC	=	hVSMC	Ma et al., 2007
(24S)-stigmasta-5,28-diene-3β,24- ol	LXR agonist	↑	U937					Castro Navas et al., 2018
(24S)-stigmasta-5-ene-3β,24-ol	LXR agonist	↑	U937					Castro Navas et al., 2018
Stigmasterol derivatives	LXR agonist	↑	U937					Marinozzi et al., 2017
T0901317	LXR agonist	↑↑	THP-1	↑	THP-1	↑	THP-1	Fukumoto et al., 2002; Murthy et al., 2002; Terasaka et al., 2003; Thomas et al., 2003; Beyer et al., 2004; Miao et al., 2004; Quinet et al., 2004, 2006; Wu et al., 2004; Panzenboeck et al., 2006; Wang et al., 2006; Delvecchio et al., 2007, 2008; Fujiyoshi et al., 2007; Sprecher et al., 2007; Dai et al., 2008; DiBlasio-Sato et al., 2008; Smith et al., 2008; Zanotti et al., 2008; Larrede et al., 2009; Verschuren et al., 2009; Mogilenko et al., 2010; Morrow et al., 2010; Yan et al., 2010; Maejima et al., 2011; Honzumi et al., 2011; Chen et al., 2012; Di et al., 2012; El Roz et al., 2012; Elali and Hermann, 2012; Jiang et al., 2012; Ma et al., 2014; Kaneko et al., 2015; Kirchgessner et al., 2015; Manna et al., 2015; Tamehiro et al., 2015; Li et al., 2016; Carter et al., 2017; Jiang and Li, 2017; Marinozzi et al., 2017; Monzel et al., 2017; Kaseda et al., 2018
		↑↑	RAW264.7	↑↑	RAW264.7	↑	HDL
		↑	J774	↑	MCF-7	↑	J774
		↑	U937	↑↑	Caco-1	↑	Caco-1
		↑↑	HepG2	↑	HL-1		HL-1
		↑↑	Caco-1	↑	TR-CSFB3	↑	apoA-I
		↑	HL-1	↑↑	haSMC^{^a}	↑	HDL
		↑↑	pBCECs	↑	Cerebral endothelial cells	↑	SAS
		↑	TR-CSFB3	↑↑	Blood-derived macrophages^{^a}	↑	Jurkat
		↑↑	SAS	↑	Aorta endothelial cells^{^c}	↑	Fu5AH
		↑↑	haSMC	↑	Liver^{^b}^,^{^k}	↑	COS-7
		↑↑	McARH7777	↑	Aorta^ⁱ^,^{^o}	↑	pBCECs
		↑↑	CD4⁺ T cells^{^a}	↑	Peripheral blood^{^e}^,^{^f}	↑	Monocyte-derived macrophages^{^a}
		↑↑	Jurkat			↑	CD4⁺ T cells^{^a}
		↑	Cerebral endothelial cells			↑	HSKMc^{^a}
		↑	Murine immortal macrop.				haSMC^{^a}
		↑	Murine neuro2A			=	apoA-I
		↑	Murine BV-2			↑	HDL
		↑	Rat C6				MCF-7
		↑↑	Blood-derived macrop^{^g}			=	apoA-I
		↑	Aorta endothelial cells^c			↑	HDL
		↑	Renal glomerular mesangial cellsⁱ			↑	Murine primary macrop.
		↑↑	PM^{^b}^,^{^d}^,^{^g}^,^{^h}			↑	PM^{^b}^,^{^d}^,^{^g}^,^{^h}
		↑↑	Liver ^{^b}^,^{^c}^,^{^h}^,^ⁱ^,^{^l}^,^{^k}			↑	Murine immortal macrop.
		↑↑	Aorta^{^b}^,^{^c}^,^ⁱ^,^{^k}^,^{^o}			↑	Renal glomerular mesangial cells^ⁱ
		↑	Small intestine^{^c}
		↑	Kidney^{^b}^,^{^h}
		↑	Duodenum^{^b}^,^{^h}
		↑	Peripheral blood^{^f}
		↑	Proximal intestine^{^k}
		↑	Distal intestine^{^k}
		↑↑	Brain^{^m}^,^ⁿ

Tacrolimus	FK-binding protein-12 inhibitor	↑=	THP-1		—		—	Jin et al., 2004
Teniposide	DNA topoisomerase II inhibitor	↑	RAW264.7	↑	PM^{^b}	↑	PM^{^b}	Zhang et al., 2013a
		↑↑	PM^{^b}			↑	RCT
		↑	THP-1
		↑	Blood monocyte
Topiramate	GABA-A receptor agonist	↑↑	MDM	↑↑	MDM		MDM	Yang et al., 2014
						↑	apoA-I
						↑	HDL
YC-1	Soluble guanylyl cyclase activator	↑↑	J774A.1	=	J774A.1	↑	J774A.1	Tsou et al., 2014
YC-1	Soluble guanylyl cyclase activator	↑	Aorta^{^c}	=	Aorta^{^c}	↑	J774A.1	Tsou et al., 2014

BMM, bone marrow– derived macrophage; BREC, bovine retinal endothelial cells; haSMC, human airway smooth muscle cells; HSKM, human skeletal muscle cells; hVSMC, human vascular smooth muscle cells; macrop, macrophage; MCF-7, Michigan Cancer Foundation-7; MDM, monocyte-derived macrophage; pBCECs, procine brain capillary endothelial cells; PBMC, peripheral blood mononuclear cell; PM, peritoneal macrophages; prox, proximal; SAS, human squamous cell carcinoma cell line.
↵^a Human.
↵^b C75BL/6 mice.
↵^c apoE^−/− C57BL/6 mice.
↵^d LXRβ^−/− C75BL/6 mice.
↵^e Cynomolgus monkeys.
↵^f Male long Evans rats.
↵^g LDLR^−/− C75BL/6 mice.
↵^h LXRα^−/− C75BL/6 mice.
↵ⁱ New Zealand White rabbits.
↵^j Male chine Bama minipigs.
↵^k Male SD rats.
↵^l 129Sv mice.
↵^m APP/PS1∆9/APOE4^+/+/ABCA1^+/− C57 BL/6 mice.
↵ⁿ APP/PS1∆9/APOE3^+/+/ABCA1^+/− C57 BL/6 mice.
↵^o E3L mice.