Table 2

Novel agents in clinical trials

Category*Therapeutic agentMechanism of actionReference
HbF augmentation Vorinostat, panobinostat HDAC inhibition 43 
Sodium dimethylbutyrate HDAC inhibition 31 
Decitabine DNA demethylation 33 
Pomalidomide Histone acetylation of γ-globin promoter 30 
Adhesion GMI-1070 Pan-selectin inhibitor 21 
IVIG Inhibits neutrophil activation and RBC capture 22, 23, 25 
SelG1 Humanized anti-P-selectin monoclonal antibody Selexys 
Heparin (tinzaparin) Inhibits P-selectin 37 
Propranolol Inhibits RBC adhesion to the endothelium 
Inflammation Regadenoson A2AR agonist, blocks iNKT activation 39 
Statins Anti-inflammatory 44 
Zileuton 5-lipoxygenase inhibitor, used in asthma 45 
Fructose-1,6-diphosphate (FDP) Reduces ischemia–induced tissue damage 46 
MP4CO PEG carboxy-hemoglobin 47 
Antiplatelet therapy Prasugrel ADP receptor blockade 42 
Eptifibatide αIIb/β3 antagonist 48 
Oxidative injury Omega-3 fatty acids  40 
Glutamine Increases NADPH 49 
NAC Increased glutathione 41 
Alpha-lipoic acid Inhibits NF-κB, increases glutathione 50 
Acetyl-L-carnitine Decreases lipid peroxidation  
Antisickling agent Aes-103 Binds sickle hemoglobin and shifts oxyhemoglobin dissociation curve to the left 51 
Viscosity Poloxamer-188 Non-ionic surfactant, improves microvascular flow 52 
Vascular tone IV magnesium Vasodilatation 53 
NO L-arginine Substrate for NO 54 
Category*Therapeutic agentMechanism of actionReference
HbF augmentation Vorinostat, panobinostat HDAC inhibition 43 
Sodium dimethylbutyrate HDAC inhibition 31 
Decitabine DNA demethylation 33 
Pomalidomide Histone acetylation of γ-globin promoter 30 
Adhesion GMI-1070 Pan-selectin inhibitor 21 
IVIG Inhibits neutrophil activation and RBC capture 22, 23, 25 
SelG1 Humanized anti-P-selectin monoclonal antibody Selexys 
Heparin (tinzaparin) Inhibits P-selectin 37 
Propranolol Inhibits RBC adhesion to the endothelium 
Inflammation Regadenoson A2AR agonist, blocks iNKT activation 39 
Statins Anti-inflammatory 44 
Zileuton 5-lipoxygenase inhibitor, used in asthma 45 
Fructose-1,6-diphosphate (FDP) Reduces ischemia–induced tissue damage 46 
MP4CO PEG carboxy-hemoglobin 47 
Antiplatelet therapy Prasugrel ADP receptor blockade 42 
Eptifibatide αIIb/β3 antagonist 48 
Oxidative injury Omega-3 fatty acids  40 
Glutamine Increases NADPH 49 
NAC Increased glutathione 41 
Alpha-lipoic acid Inhibits NF-κB, increases glutathione 50 
Acetyl-L-carnitine Decreases lipid peroxidation  
Antisickling agent Aes-103 Binds sickle hemoglobin and shifts oxyhemoglobin dissociation curve to the left 51 
Viscosity Poloxamer-188 Non-ionic surfactant, improves microvascular flow 52 
Vascular tone IV magnesium Vasodilatation 53 
NO L-arginine Substrate for NO 54 
*

Some therapies have multiple mechanisms of action.

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