Mechanism of action
Sickle cell disease is characterized by deoxygenated sickle hemoglobin (HbS) polymerization. The genetic mutation causing this disease leads to the formation of abnormal, sickle-shaped red blood cells that aggregate and block blood vessels throughout the body, causing vaso-occlusive crises.
Sickle-shaped red blood cells cannot effectively bind oxygen, thus incapable of allowing normal blood flow to organs.
Voxelotor increases Hb oxygen affinity.
It binds reversibly to hemoglobin (Hb) by forming a covalent bond with the N‐terminal valine of the α‐chain of the protein, resulting in an allosteric modification of Hb.
Voxelotor stabilizes the oxygenated Hb state and prevents HbS polymerization by increasing hemoglobin’s affinity for oxygen.
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