Target intelligence / Profile preview

Sickle Hemoglobin (HbS)

Target: HbS
Molecular classification: Hemoglobin, Protein, Mutated Protein

Overview

Sickle hemoglobin (HbS) is an abnormal variant of hemoglobin resulting from a single amino acid substitution (Glu6Val) in the beta-globin chain. This mutation causes HbS molecules to polymerize under low oxygen conditions, leading to red blood cell sickling, vaso-occlusion, chronic anemia, and organ damage characteristic of sickle cell disease. HbS is a therapeutic target for drugs aimed at reducing sickling and improving oxygen delivery.

Other names: Hemoglobin SHbSSickle cell hemoglobin

Mechanism of action

Hydroxyurea increases fetal hemoglobin production, inhibiting HbS polymerization. Voxelotor binds to hemoglobin and increases its affinity for oxygen.

Biological functions

Oxygen transportRed blood cell structure and function

Disease associations

Sickle cell diseaseAnemiaVaso-occlusionOrgan damageChronic pain

Safety considerations

Hydroxyurea: Myelosuppression, teratogenicityVoxelotor: Reversible hemoglobin increaseRisk of vaso-occlusive crisesIncreased susceptibility to infectionsPotential for pulmonary hypertensionIron overload from blood transfusions

Interacting drugs

Hydroxyurea

1 more in the full profile.

Biomarkers

HbS levelsFetal hemoglobin (HbF) levelsRed blood cell countHemoglobin concentrationMarkers of hemolysis (e.g., lactate dehydrogenase, bilirubin)

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