Introduction of voxelotor to oxygenated and deoxygenated Hb yields divergent oxygen affinities. (A) Oxygen dissociation curves for whole blood, hematocrit 20%, [Hb] = 1 mM, 86% sickle Hb. The drug was added to the blood sample at atmospheric pressure and then deoxygenated. Taken from Oksenberg et al³ with permission. (B) Oxygen association curves for sickled cells. Sickle blood was deoxygenated, and sickling was visually confirmed before voxelotor was added. Taken from Dufu et al¹¹ with permission. Note that 0.3-mM voxelotor produces a composite curve in panel A, and a simple curve in panel B. The p50 values are coincidentally similar; however, the simple curve in panel B cannot be ascribed to R-state binding, which would correspond to the very low saturated value of 1 mM in panel A. Likewise, note that at 1 mM the association curves of panel B have not changed to low p50 curves as seen in panel A.