Dalcetrapib
Dalcetrapib reduces red blood cell sickling in sickle cell disease and boosts the effect of voxelotor when combined (Clin Hemorheol Microcirc 2026)
Original title: Dalcetrapib decreases red blood cell sickling propensity in sickle cell disease
This study compared dalcetrapib and voxelotor for their effects on red blood cell rheology and hemoglobin oxygen affinity in sickle cell disease, using oxygen gradient ektacytometry to measure red blood cell deformability in normoxia and hypoxia and the propensity of cells to sickle. Both voxelotor and dalcetrapib increased red blood cell deformability under hypoxia and reduced sickling propensity during deoxygenation. Unlike voxelotor, dalcetrapib did not alter the oxygen affinity of hemoglobin S, indicating a distinct mechanism of action. Combining voxelotor and dalcetrapib produced greater rheological improvement than either drug alone, suggesting dalcetrapib could inhibit red blood cell sickling during deoxygenation through a pathway complementary to the oxygen-affinity effect of voxelotor.
Original abstract
The aim of the present study was to compare the effects of dalcetrapib and voxelotor on the rheology of red blood cells (RBCs) from sickle cell patients, as well as on hemoglobin oxygen affinity. Oxygen gradient ektacytometry was used to determine RBC deformability in normoxia and hypoxia, as well as the propensity of RBCs to sickle. Hemoglobin oxygen affinity was also measured following dalcetrapib and voxelotor incubation. Both voxelotor and dalcetrapib increased RBC deformability in hypoxia and decreased the propensity of RBCs to sickle under deoxygenation. However, in contrast to voxelotor, the affinity of hemoglobin S (HbS) to oxygen was not affected by dalcetrapib. The combination of both voxelotor and dalcetrapib led to greater RBC rheological improvement. Our findings suggest that dalcetrapib could inhibit RBC sickling during deoxygenation.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.