Voxelotor (GBT440)

Voxelotor (GBT440) (CAS No.: 1446321-46-5) is a synthetic small molecule hemoglobin modulator and hemoglobin S polymerization inhibitor used as a biochemical tool in hematology and translational pharmacology research, with a primary application in mechanistic studies of sickling biology and anti polymerization drug discovery workflows. In experimental systems, it is characterized by direct interaction with hemoglobin, including binding at the N terminal valine region of the alpha chain, which increases oxygen affinity and stabilizes the oxygenated conformation to reduce deoxygenation driven hemoglobin S polymer assembly, thereby supporting pathway level investigation of erythrocyte deformation, oxidative stress coupling, and hypoxia responsive cellular injury processes. Available research descriptions place its functional potency within broadly reported nanomolar to micromolar activity contexts depending on assay format, protein state, and readout endpoint, and it is commonly profiled alongside metabolism and transporter panels, including cytochrome P450 associated interaction assessments such as CYP3A4 related studies, to define exposure response relationships in preclinical settings. Typical uses include in vitro erythrocyte or blood based phenotypic assays, ex vivo sickling and rheology measurements, and in vivo proof of mechanism studies in relevant animal models of hemoglobinopathy biology, while concentrations or doses used in experiments typically depend on specific experimental designs and research objectives.