Table 1.

Various extracellular and intracellular RAGE binding ligands with their clinical implications

Ligand	Type	Binding domain	Binding affinity	Clinical implication	References
AGEs (MG-H1)	Extracellular ligand	V	ND	Cardiovascular diseases (atherosclerosis), Diabetes, cancer, chronic inflammation	(Xue et al., 2011) (Heier et al., 2015; Wetzels et al., 2019; S. I. Yamagishi, 2019)
S100B	Extracellular ligand	VC1 VC1 V	3.2–9.4 μM (ITC) Kd1 = 11 nM, Kd1 = 244 nM (SPR) Kd1 = 550 nM, Kd2 = 470 nM (SPR)	Inflammatory response and Neuronal disease, Down syndrome, Alzheimer’s disease.	(Chen et al., 2020; Esposito et al., 2008) (Dattilo et al., 2007)
S100P	Extracellular ligand	V	6 μM	Cancer disease and chronic inflammation	(Penumutchu, Chou, & Yu, 2014), (M. Lin et al., 2021)
S100A6	Extracellular ligand	VC1 V C2	0.6–5.8 μM 0.5–13.5 μM 28 nM to 1 μM	Alzheimer’s disease (AD), epileptogenesis, amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and Parkinson’s disease (PD)	(Leclerc, Fritz, Weibel, Heizmann, & Galichet, 2007), (Filipek & Lesniak, 2020)
S100A11	Extracellular ligand	V	0.5 μM (Immunofluorescence assay)	Cancer, Neurological diseases, Vascular calcification, and inflammatory diseases.	(Zhang, Zhu, Miao, & Liang, 2021) and (Huang, Chou, & Yu, 2016)
S100A12	Extracellular ligand	C1 V	70 nM 3.1 μM (Immunofluorescence assay)	Cardiovascular diseases, Inflammatory response, and cancer progression	(Saito et al., 2012; Wang et al., 2020; Xie et al., 2007) (Chiou, Fu, Chou, & Yu, 2016)
Amyloid-β	Extracellular ligand	V & C1	70–80 nM	Neurodegenerative disorders (Alzheimer’s disease)	(Deane et al., 2012)
Quinolinic acid	Extracellular ligand	VC1	43 nM	Huntington’s disease, hepatic encephalopathy, AIDS-dementia complex, and Alzheimer’s disease	(Schwarcz, Bruno, Muchowski, & Wu, 2012; Serratos et al., 2015)
HMGB1	Extracellular ligand	VC1C2	6–10 nM	Chronic inflammation and cancer	(Hori et al., 1995; Sims, Rowe, Rietdijk, Herbst, & Coyle, 2010)
DNA/RNA	Extracellular ligand	VC1	ND	Chronic inflammation	(Sirois et al., 2013)
RSV F-protein	Extracellular ligand	VC1	Very low binding (Alpha Screen assay	Modulates lower respiratory tract infection	(Tian et al., 2013)
Longistatin	Extracellular ligand	V	72 nM	Acts as an antagonist and can reduce the inflammation	(Anisuzzaman et al., 2014)
TIRAP	Intracellular ligand	Cytoplasmic domain	ND	Chronic inflammation	(Rajpoot et al., 2021)
DIAPH1	Intracellular ligand	Cytoplasmic domain	4–8 μM	Diabetes, cardiovascular diseases	(Egana-Gorrono et al., 2020; Rai et al., 2012)
ERK1/2	Intracellular ligand	Cytoplasmic domain	ND	Cancer and chronic inflammation	(Ishihara et al., 2003)
DOCK7	Intracellular ligand	Cytoplasmic domain	ND	Cancer and chronic inflammation	(Yamamoto et al., 2013)
C1q	Unknown	Unknown	ND	Recruitment of phagocytosis	(Ma et al., 2012)
PS	Unknown	Unknown	ND	Alveolar macrophagic Rac1 activation	(He et al., 2011)