Table 2.

Examples of promising therapeutic approaches targeting ischemia and reperfusion

Intervention	Target	Potential downside	Stage	Reference
TAK-242	Inhibition of TLR4	Immune suppression, worsening of bacterial infections	Phase 2 clinical trial in acute respiratory failure; preclinical studies in ischemia and reperfusion	25,26
T cell–based approaches	Suppression of γδ T cells; expansion of Treg cells	Unclear	Preclinical	37,39,40,42
Fibrinogen split product Bβ15–42	Unclear	Unclear	Phase 2 clinical trial	15,56,57
Cyclosporine	Inhibition of apoptosis	Immune suppression; worsening of bacterial infection	Phase 2 clinical trial	66
Chloramphenicol	Activation of autophagy	Bone marrow toxicity (bone marrow suppression or aplastic anemia)	Preclinical (large animal study)	69
PHD inhibitors	Inhibition of the oxygen sensing PHD enzymes resulting in HIF stabilization	Unclear	Phase 2 clinical trial in renal anemia; preclinical studies in ischemia and reperfusion	79,92-94
Ischemic preconditioning	Multiple (for example, adenosine signaling, HIF stabilization and attenuation of inflammation)	Unclear	Phase 2 clinical trial	79-83
Ischemic postconditioning	Multiple	Unclear	Phase 2 clinical trial	87,88
Remote ischemic conditioning	Multiple	Unclear	Phase 2 clinical trial	89
Nitric oxide (NO)	Multiple	Elevation of methemoglobin	Phase 2 clinical trial	106,107
Apyrase	ATP breakdown (attenuation of ATP signaling and promotion of adenosine generation and signaling)	Unclear	Preclinical	81,120
Nucleotidase	AMP conversion to adenosine; enhanced adenosine generation and signaling	Unclear	Preclinical	80,122,123
Regadenoson, ATL146e	Specific adenosine receptor agonists targeting Adora2a	Unclear	Phase 1 trial ongoing	3,131
Bay 60-6583	Specific adenosine receptor agonist targeting Adora2b	Sickling of red blood cells in individuals with sickle cell disease	Preclinical	80,129,130
Inhibitors of miR-92a	Promotion of angiogenesis	Unclear	Preclinical	137
Activators of miR-499 or miR-24	Inhibition of apoptosis	Unclear	Preclinical	138,139