Table 1.

Drug candidates exhibiting benefits in sickle cell disease

Drug name	Action mechanism	Reference
Butyrate	HDAC inhibition, mood stabilization	[110, 111]
Decitabine	DNA demethylation	[112]
Trichostatin A	Increases HbF level; decrease adhesion of cells to vessel wall	[113]
Pomalidomide	Gammaglobin activation by Histone deacetylase	[114]
Senicapoc	Improves RBC hydration	[115]
Nitric Oxide	Increase NO	[116]
Tinzaparin	Decreases P-selectin-mediated acute pain episodes	[117]
6R-BH4	Increases NO; improve endothelial function	[118, 119]
Sidenafil	Increases NO	[116]
Eptifibatide	Decreases platelet aggregation and decreases CD40 ligand release	[120]
Statins	Improves endothelial function	[121]
Dexmethasone	Decrease inflammation	[122]
Nix-0699	Uncertain, but inhibits acute painful crisis	[44, 123, 124]
Intravenous immunoglobulin (IVIG)	Decreases the number of leukocytes & acute pain episodes	[44, 123, 124]
Vorinostat, panobinostat	HDAC inhibition	[113]
GMI-1070	Pan-selectin inhibitor	[45]
Propranolol	Inhibits RBC adhesion to the endothelium	[125]
Regadenoson	A2AR agonist, blocks iNKT activation	[126]
Zileuton	5-lipoxygenase inhibitor, used in asthma	[127]
Fructose-1,6-diphosphate (FDP)	Reduces ischemia–induced tissue damage	[128]
Prasugrel	ADP receptor blockade	[129]
MP4CO	PEG carboxy-hemoglobin	[130]
Acetyl-L-carnitine	Decreases lipid peroxidation	[90]
Alpha-lipoic acid	Inhibits NFkB, increases glutathione	[131]
NAC	Increased glutathione	[132]
Omega-3 fatty acids	Decreases VOC events	[18]
Glutamine	Increases NADPH	[133]
IV magnesium	Vasodilatation	[134]
Aes-103	Binds sickle hemoglobin and shifts oxy-hemoglobin dissociation curve to the left	[90]
Poloxamer-188	Non-ionic surfactant, improves micro-vascular flow	[135]
L-arginine	Substrate for NO	[116]

HbF fetal hemoglobin, NO nitric oxide, RBC red blood cell, IVIG intravenous immunoglobulin, HDAC Histone deacetylases, Nix-0699 Niprisan, GMI-1070 Rivipansel, FDP Fructose-1,6-diphosphate, NADPH Nicotinamide adenine dinucleotide phosphate, A2AR Adenosine A_2A receptor, PEG Polyethylene glycol, ADP Adenosine diphosphate, iNKT Invariant natural killer T cells

Few drug candidates may exhibit multiple mechanisms of action