Table 1 Drug candidates exhibiting benefits in sickle cell disease

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]