Table 2.

Pharmacological therapies currently in use that target TLR4 and its downstream signalling

Compound	Description	Target	Mechanism of action	Disease model or cell type tested	Main outcome (reference)
Eritoran (E5564)	Synthetic LPS lipid A analogue	MD2	Competitively binds a large pocket of MD2	Rat model of kidney ischaemia/reperfusion	Ameliorated kidney ischaemia/reperfusion‐related inflammatory responses (Liu et al., 2010a)
SPA4	Peptide	TLR4	Binds to surfactant A and blocks TLR4 activation	HEK293 cells	Decreased secretion of pro‐inflammatory cytokines (Ramani et al., 2013)
TAK‐242	Small molecule/cyclohexene inhibitor	TLR4	Binds TIR domain and affects the recruitment of adapters	Rat model of hyperaldosteronism	Inhibited hypertension and cardiac and renal fibrosis and attenuates aldosterone‐induced epithelial–mesenchymal transition (Zhang et al., 2015)
				Rat VSMCs	Decreased NADPH oxidase activity, superoxide anion production and cell migration and proliferation (De Batista et al., 2014)
				Mouse model of hypertension (AngII)	Reduced AngII‐induced increase in phospho‐JNK1/2 and p65 NF‐κB subunit nuclear protein expression (Hernanz et al., 2015)
NI‐0101	Monoclonal antibody	TLR4	Antagonist	Synovial explant culture model	Decreased pro‐inflammatory cytokine secretion (TNF‐α and IL‐6) (Page et al., 2011)
Valsartan	AT1 – AngII receptor blocker	TLR4	Unknown	Rat model of myocardial ischaemia/reperfusion	Improved myocardial injury, such as smaller infarct size, and decreased release of myocardial enzymes and pro‐inflammatory mediators (Yang et al., 2009a)
Candesartan	AngII receptor blocker	TLR4	AngII receptor independent	Rat mesangial cells	Decreased oxidative stress and exerted anti‐apoptotic effects (Lv et al., 2009)
Fluvastatin	HMG‐CoA reductase inhibitor	TLR4	Inhibits NF‐κB activation	Rat model of myocardial ischaemia/reperfusion	Decreased ischaemic injury and inhibited the expression levels of TLR4, TNF‐α and NF‐κB (Yang et al., 2011)
Atorvastatin	HMG‐CoA reductase inhibitor	TLR4	Impairs TLR4 recruitment of lipid raft and inhibits NF‐κB activation	Rabbit model of atherosclerosis	Impaired TLR4/NF‐κB activation in atherosclerotic plaques that decreased inflammation (Fang et al., 2014)
ST2825	Peptidomimetic	MyD88	Inhibits homodimerization of MyD88	Mouse model of hypertension (AngII)	Decreased NADPH oxidase activity (Hernanz et al., 2015)
dnMyD88	Mutated form of MyD88	MyD88	Inhibits homodimerization of MyD88	Rat model of myocardial ischaemia/reperfusion	Prevented ischaemia/reperfusion via inhibition of NF‐κB (Ha et al., 2006)

HMG‐CoA, hydroxymethylglutaryl CoA.