Hemoglobin S modulator
Hemoglobin S oxygen-affinity modulator (anti-sickling)
- Stabilizes the oxygen-bound (R) state
- Oxygenated HbS does not polymerize → less sickling and hemolysis
- Left-shifted O₂ curve → ↓ tissue oxygen delivery
Drugs with this mechanism (1)
- Voxelotor — Hemoglobin-S polymerization inhibitor formerly used for sickle cell disease; withdrawn worldwide in 2024 over safety concerns.
Self-check
- Which hemoglobin conformational state is stabilized by increased HbS oxygen affinity?
The oxygen-bound R state. - What oxygen-delivery tradeoff follows the left-shifted dissociation curve?
Reduced tissue oxygen delivery.
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