Voxelotor (GBT 440) is a novel hemoglobin S (HbS) polymerization inhibitor primarily used for the treatment of sickle cell disease (SCD) and a cytochrome P450 3A4 inhibitor. Voxelotor targets and covalently binds to the N-terminal valine of the HbS alpha chain, thereby stabilizing sickle cell hemoglobin (HbS).

ERG (human):> 10 μM

METHODS: Voxelotor (3-30 µmol/L) was incubated with hemoglobin (25 µmol/L) in TES or saline buffer at 37 ℃ for 45 min, and changes in the binding affinity of O2 for Hb were measured using a TCS hematology analyzer.
RESULTS: Voxelotor, a small molecule that binds to the N-terminal α-chain of Hb, increases the affinity of HbS for oxygen, delays HbS polymerization in vitro and prevents erythrocyte sickling. [1]
METHODS: HepG2 cells were treated with Voxelotor (1 µg/mL) and their metabolites were analyzed by liquid chromatography, high-resolution MS and tandem MS.
RESULTS: Voxelotor can be used for the identification of phase I and phase II metabolites in vitro. [2]

METHODS: To assess the activity and efficacy of Voxelotor, Voxelotor (100-150 mg/kg, 0.5% methylcellulose/0.5% SDS) was administered by gavage to a mouse model of SCD twice daily for 9-12 days.
RESULTS: Voxelotor reduced isolated sickle cells and prolonged erythrocyte half-life in the SCD mouse model. [1]