Voxelotor (GBT-440; Oxbryta)

Description: Voxelotor (formerly known as GBT-440; trade name: Oxbryta) is a potent and orally bioactive allosteric effector of sickle cell hemoglobin. It increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, Voxelotor binds with a 1:1 stoichiometry. Voxelotor is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of ?150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. In November 2019, voxelotor received accelerated approval in the United States for the treatment of sickle cell disease (SCD) for those 12 years of age and older. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

References: ACS Med Chem Lett. 2017 Jan 23; 8(3):321-326.